Lysosomal Trafficking and Cysteine Protease Metabolism Confer Target-specific Cytotoxicity by Peptide-linked Anti-CD30-Auristatin Conjugates

Name: Work Video:
Duration: 3 min 30 s
May S.K. Sutherland; Russell J. Sanderson; Kristine A. Gordon; Jamie B. Andreyka; Charles G. Cerveny; Changpu Yu; Timothy S. Lewis; Damon L. Meyer; Roger F. Zabinski; Svetlana O. Doronina; Peter D. Senter; Che‐Leung Law; Alan F. Wahl
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'https://openalex.org/W2121080375', 'https://openalex.org/W2129901781', 'https://openalex.org/W2131478662', 'https://openalex.org/W2136101268', 'https://openalex.org/W2139275843', 'https://openalex.org/W2143459780', 'https://openalex.org/W2143586703', 'https://openalex.org/W2150694237', 'https://openalex.org/W2154625078', 'https://openalex.org/W2156506990', 'https://openalex.org/W2171368669', 'https://openalex.org/W311717631', 'https://openalex.org/W4248206010'], 'related_works': ['https://openalex.org/W2491126842', 'https://openalex.org/W2373981509', 'https://openalex.org/W2122197456', 'https://openalex.org/W2033947618', 'https://openalex.org/W2030198142', 'https://openalex.org/W2011205061', 'https://openalex.org/W2006880939', 'https://openalex.org/W1998473336', 'https://openalex.org/W1997721019', 'https://openalex.org/W1577699370'], 'abstract_inverted_index': {'The': [0, 253, 533, 604, 1975, 2102, 2118, 2224, 2422, 2544, 2776, 2869, 2883, 2899, 2928, 3107, 3119, 3148, 3334, 3420, 3433, 3481, 3569, 3701, 3850, 4268, 4299, 4379], 'chimeric': [1, 254, 1853], 'anti-CD30': [2, 255, 976, 1648, 1773, 1854], 'monoclonal': [3, 256, 563, 571], 'antibody': [4, 80, 119, 257, 333, 372, 1855, 2143, 2177, 2220, 2431, 2446, 2540, 2674, 2977, 2987, 3170, 3175, 3968, 4023, 4227, 4330], 'cAC10,': [5, 258, 2038, 2511], 'linked': [6, 259, 589, 616, 2676], 'to': [7, 65, 102, 127, 215, 217, 260, 318, 355, 380, 468, 470, 549, 559, 590, 596, 617, 700, 912, 1005, 1102, 1173, 1409, 1418, 1816, 1889, 1969, 2144, 2166, 2200, 2215, 2408, 2537, 2611, 2645, 2677, 2864, 3164, 3171, 3347, 3415, 3428, 3472, 3477, 3531, 3580, 3593, 3683, 3802, 3978, 3986, 3995, 4003, 4012, 4031, 4036, 4041, 4079, 4218, 4256, 4331, 4422], 'the': [8, 61, 71, 78, 118, 128, 148, 173, 194, 206, 218, 247, 261, 314, 324, 331, 371, 381, 401, 426, 447, 459, 471, 500, 508, 515, 560, 618, 627, 701, 707, 861, 873, 877, 975, 1006, 1176, 1399, 1403, 1410, 1432, 1436, 1443, 1459, 1583, 1588, 1592, 1700, 1767, 1805, 1817, 1820, 1829, 1985, 2058, 2134, 2180, 2218, 2452, 2458, 2465, 2484, 2528, 2530, 2672, 2704, 2831, 2867, 2936, 2942, 2951, 2965, 2976, 2984, 3027, 3063, 3095, 3167, 3207, 3213, 3339, 3342, 3416, 3429, 3444, 3473, 3520, 3548, 3574, 3594, 3685, 3853, 3857, 3881, 3922, 3931, 3935, 3965, 4020, 4051, 4133, 4182, 4192, 4202, 4225, 4235, 4238, 4246, 4258, 4273, 4285, 4369, 4376, 4423], 'antimitotic': [9, 262], 'agents': [10, 263, 3602], 'monomethyl': [11, 264, 574, 578, 1009, 1931], 'auristatin': [12, 265, 575, 579, 1010, 1809, 1932], 'E': [13, 266, 1011], '(MMAE)': [14, 267], 'or': [15, 156, 162, 185, 268, 409, 415, 438, 593, 696, 703, 858, 927, 1454, 1510, 2040, 2061, 2178, 2386, 2411, 2416, 2513, 2520, 2706, 2715, 2972, 3049, 3065, 3097, 3103, 3132, 3227, 3328, 3405, 3550, 4067, 4073, 4275, 4280, 4291, 4308, 4343, 4398], 'F': [16, 269, 1933], '(MMAF),': [17, 270], 'produces': [18, 271], 'potent': [19, 272, 619, 1181, 3600, 3898], 'and': [20, 27, 46, 49, 75, 81, 86, 98, 105, 113, 120, 193, 200, 222, 233, 273, 280, 299, 302, 328, 334, 339, 351, 358, 366, 373, 446, 453, 475, 486, 529, 552, 681, 687, 854, 864, 1108, 1170, 1182, 1189, 1356, 1412, 1439, 1604, 1647, 1653, 1707, 1754, 1769, 1776, 1781, 1795, 1800, 1819, 1847, 1851, 1887, 1930, 1972, 2025, 2051, 2113, 2125, 2153, 2205, 2393, 2464, 2494, 2541, 2548, 2552, 2593, 2631, 2685, 2721, 2730, 2784, 2803, 2860, 2887, 2907, 2935, 2964, 3078, 3141, 3179, 3209, 3443, 3529, 3590, 3707, 3796, 3805, 3856, 3860, 3871, 3954, 4053, 4057, 4069, 4089, 4137, 4141, 4146, 4159, 4187, 4208, 4211, 4228, 4237, 4261, 4288, 4294, 4304, 4321, 4352, 4360, 4366, 4372, 4382, 4408, 4416, 4419], 'highly': [21, 274, 1104, 1542, 3599], 'CD30-selective': [22, 275], 'anti-tumor': [23, 276, 1534], 'activity': [24, 277, 1821, 2946, 3914], 'in': [25, 28, 44, 107, 172, 213, 278, 281, 297, 360, 425, 466, 514, 519, 691, 869, 904, 925, 1106, 1109, 1426, 1465, 1599, 1642, 1656, 1783, 2015, 2057, 2110, 2503, 2703, 2760, 2817, 2845, 2904, 3051, 3062, 3094, 3114, 3157, 3352, 3462, 3507, 3525, 3547, 3800, 4045, 4245], 'vitro': [26, 279, 1107], 'vivo.': [29, 282], 'These': [30, 209, 283, 462, 850, 919, 1826], 'drugs': [31, 55, 284, 308, 3855, 3878], 'are': [32, 228, 285, 481, 866], 'appended': [33, 286, 1004], 'via': [34, 287, 1013], 'a': [35, 108, 235, 288, 361, 488, 971, 1014, 1982, 2232, 2409, 2440, 2632, 2664, 2745, 3115, 3189, 3349, 3584, 3710, 4046], 'valine-citrulline': [36, 289, 1016], '(vc)': [37, 290, 1017], 'dipeptide': [38, 291], 'linkage': [39, 292], 'designed': [40, 293], 'for': [41, 230, 238, 246, 294, 483, 491, 499, 537, 543, 626, 1757, 1840, 1845, 1992, 2042, 2054, 2127, 2146, 2193, 2401, 2429, 2492, 2515, 2521, 2697, 2770, 2790, 2842, 2877, 2893, 2922, 2941, 3040, 3091, 3411, 3424, 3440, 3448, 3465, 3504, 3576, 4076, 4139, 4284, 4297, 4306, 4363, 4388], 'high': [42, 295, 923], 'stability': [43, 296, 924], 'serum': [45, 298, 926], 'conditional': [47, 300], 'cleavage': [48, 301], 'putative': [50, 303], 'release': [51, 174, 232, 304, 427, 485, 932, 1419, 1441, 1760], 'of': [52, 77, 131, 138, 150, 154, 175, 197, 205, 250, 305, 330, 384, 391, 403, 407, 428, 450, 458, 503, 512, 562, 600, 629, 706, 876, 916, 922, 974, 1392, 1442, 1450, 1539, 1772, 1798, 1807, 1822, 1832, 1984, 2005, 2065, 2451, 2455, 2708, 2948, 2953, 2967, 3029, 3067, 3099, 3212, 3344, 3418, 3431, 3475, 3533, 3552, 3598, 3690, 3705, 3852, 3876, 3924, 3952, 3967, 4022, 4055, 4144, 4156, 4185, 4191, 4224, 4233, 4248, 4324], 'fully': [53, 306], 'active': [54, 307, 1444], 'by': [56, 136, 168, 243, 309, 389, 421, 496, 934, 1415, 1835, 1997, 2228, 2437, 2622, 2726, 2957, 2979, 3111, 3199, 3239, 3246, 4148, 4240], 'lysosomal': [57, 165, 225, 310, 418, 478, 935, 1416, 1823, 2943, 3479], 'cathepsins.': [58, 311], 'To': [59, 312, 2130, 2174, 3205, 3361, 4049], 'characterize': [60, 313], 'biochemical': [62, 315], 'processes': [63, 316], 'leading': [64, 317, 510], 'effective': [66, 319, 539, 1183, 1543, 1758, 3887], 'drug': [67, 143, 231, 320, 396, 484, 857, 906, 931, 1097, 1394, 1452, 1759, 1833, 2542, 2968, 3910], 'delivery,': [68, 321], 'we': [69, 322, 968, 1765, 1802], 'examined': [70, 323], 'intracellular': [72, 203, 244, 325, 456, 497, 1770, 4142, 4168, 4231, 4380], 'trafficking,': [73, 326, 1438], 'internalization,': [74, 327, 1437], 'metabolism': [76, 192, 329, 445, 3028], 'parent': [79, 332], 'two': [82, 335, 1777], 'antibody-drug': [83, 121, 190, 240, 336, 374, 443, 493, 3703], 'conjugates,': [84, 337, 1779, 3031], 'cAC10vc-MMAE': [85, 155, 338, 408, 1780, 1971, 2767, 3048, 3090, 3501, 3859, 3900, 3953], 'cAC10vc-MMAF,': [87, 340, 1782, 1973], 'following': [88, 341, 2598, 3940], 'CD30': [89, 342, 1221, 2456, 4016], 'surface': [90, 343, 1405, 1434, 2453, 4154, 4183], 'antigen': [91, 344], 'interaction': [92, 345, 1430, 3807], 'with': [93, 158, 163, 346, 411, 416, 631, 872, 929, 1455, 1699, 1837, 2019, 2035, 2048, 2106, 2138, 2156, 2163, 2184, 2188, 2207, 2217, 2243, 2414, 2439, 2508, 2534, 2550, 2600, 2608, 2624, 2642, 2654, 2663, 2687, 2728, 2744, 2763, 2781, 2909, 2970, 2983, 3045, 3087, 3123, 3152, 3166, 3329, 3355, 3373, 3437, 3485, 3500, 3566, 3573, 3808, 4065, 4071, 4163, 4166, 4176, 4272, 4344, 4386, 4399], 'target': [94, 103, 124, 198, 347, 356, 377, 451, 602, 862, 1461], 'cells.': [95, 348, 603, 2868], 'Both': [96, 349], 'cAC10': [97, 350, 978, 1775, 1856, 2145, 2415, 2592, 2673, 3702, 3795, 4056, 4226], 'its': [99, 352, 2594, 4058], 'conjugates': [100, 122, 241, 353, 375, 494, 685, 689, 1448, 1538, 2418, 2595, 3704, 3858, 4239], 'bound': [101, 354, 3970, 4025], 'cells': [104, 125, 199, 357, 378, 452, 551, 1188, 1659, 2012, 2028, 2103, 2135, 2181, 2225, 2240, 2423, 2498, 2531, 2545, 2689, 2743, 2753, 2777, 3357, 3366, 3434, 3455, 3476, 3536, 3570, 3804, 3810, 4062, 4134, 4265, 4269, 4300, 4371], 'internalized': [106, 359, 2176, 2430, 4175, 4259, 4418], 'similar': [109, 362, 4177], 'manner.': [110, 363], 'Subcellular': [111, 364, 2751], 'fractionation': [112, 170, 365, 423], 'immunofluorescence': [114, 367], 'studies': [115, 368, 1827], 'demonstrated': [116, 369, 1650], 'that': [117, 142, 212, 370, 395, 465, 545, 1398, 1804, 2433, 3603, 3794, 3880, 3921, 4173, 4413], 'entering': [123, 376], 'migrated': [126, 379], 'lysosomes.': [129, 382], 'Trafficking': [130, 383], 'both': [132, 385, 1645, 3177, 4157, 4234, 4364, 4414], 'species': [133, 386], 'was': [134, 387, 1100, 1595, 1857, 1995, 2435, 2481, 2675, 2871, 2885, 2902, 3038, 3185, 3216, 3244, 3498, 3561, 3884, 3895, 3945, 4254, 4358], 'blocked': [135, 189, 388, 442, 3151], 'inhibitors': [137, 390, 1797, 2246, 2389, 2710], 'clathrin-mediated': [139, 392], 'endocytosis,': [140, 393], 'suggesting': [141, 394, 4172, 4412], 'conjugation': [144, 397], 'does': [145, 398], 'not': [146, 183, 399, 436, 1762, 3182, 4410], 'alter': [147, 400], 'fate': [149, 402, 1771], 'antibody-antigen': [151, 404], 'complexes.': [152, 405], 'Incubation': [153, 406], 'cAC10vc-MMAF': [157, 410, 2041, 2514, 3050, 3861, 3894, 3955], 'purified': [159, 412, 3032], 'cathepsin': [160, 220, 413, 473, 3033], 'B': [161, 221, 414, 474, 3034], 'enriched': [164, 417], 'fractions': [166, 419, 2794, 2938, 3082, 3482, 3521], 'prepared': [167, 420, 2796, 3715], 'subcellular': [169, 422, 1793, 2244], 'resulted': [171, 424], 'active,': [176, 429], 'free': [177, 430, 856, 1420, 3691, 3854, 3877], 'drug.': [178, 431, 1421, 3173], 'Cysteine': [179, 432], 'protease': [180, 187, 433, 440, 2388, 3072], 'inhibitors,': [181, 188, 434, 441], 'but': [182, 435, 4214], 'aspartic': [184, 437], 'serine': [186, 439], 'conjugate': [191, 444, 1594, 3911], 'ensuing': [195, 448], 'cytotoxicity': [196, 449, 1806], 'yielded': [201, 454], 'enhanced': [202, 455], 'levels': [204, 457, 3962, 4017, 4143, 4155, 4169, 4184, 4194, 4198, 4216, 4232, 4243], 'intact': [207, 460], 'conjugates.': [208, 461, 2543], 'findings': [210, 463], 'suggest': [211, 464], 'addition': [214, 467, 3417, 3430], 'trafficking': [216, 469, 1755, 1768, 1799, 2245, 2709, 4052], 'lysosomes,': [219, 472, 1411], 'perhaps': [223, 476], 'other': [224, 477, 683, 2237, 2670, 3075, 3452], 'cysteine': [226, 479, 1824, 2387, 3071], 'proteases': [227, 245, 480, 498, 936, 1417], 'requisite': [229, 482], 'provide': [234, 487, 597], 'mechanistic': [236, 489], 'basis': [237, 490, 1831], 'developing': [239, 492], 'cleavable': [242, 495], 'targeted': [248, 501], 'delivery': [249, 502, 1395, 1815, 1834], 'anti-cancer': [251, 504, 1841], 'therapeutics.': [252, 505, 1842], 'Cancer': [506, 525, 527, 745, 776, 840, 896, 997, 1128, 1160, 1313, 1346, 1380, 1488, 1503, 1572, 1631, 1880, 2301, 2582, 3013, 3318], 'is': [507, 624, 911, 1397, 1761, 1811, 3927], 'second': [509], 'cause': [511], 'mortality': [513], 'United': [516], 'States,': [517], 'resulting': [518, 903, 1177, 1598, 2900], '>500,000': [520], 'American': [521, 3541], 'deaths': [522], 'annually.': [523], '2American': [524], 'Society': [526], 'Facts': [528], 'Figures,': [530], 'available': [531], 'online.': [532], 'unmet': [534], 'medical': [535], 'need': [536], 'more': [538, 3886, 3897], 'anticancer': [540], 'therapeutics,': [541], 'especially': [542], 'strategies': [544], 'can': [546, 1462, 3693], 'focus': [547], 'toxicity': [548], 'tumor': [550, 708, 1187, 1190, 1658, 3958], 'away': [553], 'from': [554], 'normal': [555], 'tissues,': [556], 'has': [557], 'lead': [558], 'development': [561, 692], 'antibodies': [564, 4085], '(mAbs)': [565], '3The': [566], 'abbreviations': [567], 'used': [568, 625, 4255], 'are:': [569], 'mAb,': [570], 'antibody;': [572], 'MMAE,': [573, 3684], 'E;': [576], 'MMAF,': [577], 'F;': [580], 'vc,': [581], 'valine-citrulline;': [582], 'ADC,': [583, 2133, 2179, 4059], 'mAb-drug': [584, 684], 'conjugate;': [585], 'PBS,': [586, 2050, 2108, 2186, 2783], 'phosphate-buffered': [587], 'saline.': [588], 'immunotoxins,': [591], 'radionuclides,': [592], 'cytotoxic': [594, 1445], 'drugs,': [595], 'selective': [598], 'elimination': [599], 'antigen-positive': [601, 1186], 'first': [605, 4203], 'such': [606], 'clinically': [607], 'approved': [608], 'agent,': [609, 1008], 'Gemtuzumab': [610], 'ozogamicin': [611], '(Mylotarg),': [612], 'an': [613, 3891, 4329], 'anti-CD33': [614], 'mAb': [615, 878, 977, 1585, 1646, 1774, 4066, 4145, 4158, 4186, 4236, 4260, 4274, 4307, 4365, 4381, 4415], 'DNA': [620, 2732], 'damaging': [621], 'agent': [622], 'calicheamicin,': [623], 'treatment': [628], 'patients': [630], 'relapsed': [632], 'acute': [633], 'myeloid': [634], 'leukemia': [635], '(1Sievers': [636], 'E.L.': [637], 'Larson': [638], 'R.A.': [639, 772, 940, 1196], 'Stadtmauer': [640], 'E.A.': [641], 'Estey': [642], 'E.': [643, 1267, 1361, 1523, 1948, 2079, 2274, 2331, 3660, 3770], 'Lowenberg': [644], 'B.': [645], 'Dombret': [646], 'H.': [647, 811, 1377], 'Karanes': [648], 'C.': [649, 713, 758, 794, 813, 1283, 1299, 1367, 1369, 1371, 1519, 2882], 'Theobald': [650], 'M.': [651, 809, 1275, 1279, 1483], 'Bennett': [652], 'J.M.': [653, 819, 1517, 2256], 'Sherman': [654, 739], 'M.L.': [655, 740], 'Berger': [656, 737], 'M.S.': [657, 738], 'Eten': [658, 741], 'C.B.': [659, 742, 994, 1038, 1082, 1247, 1338, 1564, 1623, 1685, 1734, 1877, 1916, 2574, 3005, 3274, 3310, 3628, 3738, 3836, 4111], 'Loken': [660], 'M.R.': [661], 'van': [662], 'Dongen': [663], 'J.J.': [664, 1303], 'Bernstein': [665], 'I.D.': [666], 'Appelbaum': [667], 'F.R.': [668], 'J.': [669, 717, 719, 760, 799, 822, 1144, 1365, 1479, 2085, 2090, 2257, 2275, 2319, 2347], 'Clin.': [670, 775, 823, 839, 895, 1127, 1159, 1345, 1571, 1630, 2581, 3012, 3317], 'Oncol.': [671, 824], '2001;': [672, 2289, 2303], '19:': [673], '3244-3254Crossref': [674], 'PubMed': [675, 724, 751, 828, 845, 960, 1052, 1091, 1165, 1216, 1256, 1351, 1385, 1494, 1528, 1577, 1636, 1694, 1743, 1925, 1964, 2097, 2266, 2281, 2292, 2323, 2338, 2353, 2587, 3018, 3288, 3323, 3642, 3676, 3752, 3786, 3845, 4125], 'Scopus': [676, 725, 752, 829, 846, 961, 1053, 1092, 1166, 1217, 1257, 1352, 1386, 1495, 1578, 1637, 1695, 1744, 1926, 1965, 2098, 2293, 2324, 2339, 2354, 2588, 3019, 3289, 3324, 3643, 3677, 3753, 3787, 3846, 4126], '(743)': [677], 'Google': [678, 727, 754, 781, 831, 848, 901, 963, 1002, 1055, 1094, 1133, 1168, 1219, 1259, 1318, 1354, 1388, 1497, 1508, 1529, 1580, 1639, 1697, 1746, 1885, 1928, 1967, 2100, 2267, 2282, 2295, 2306, 2326, 2341, 2356, 2590, 3021, 3291, 3326, 3645, 3679, 3755, 3789, 3848, 4128], 'Scholar).': [679, 849, 964, 1095, 1581, 1640, 1747, 2101, 2591, 2829, 3022, 3680, 3790, 3849, 4129], 'Mylotarg': [680], 'multiple': [682, 1174, 3916], '(ADCs)': [686], 'mAbtoxin': [688], 'currently': [690], 'use': [693], 'primarily': [694], 'disulfide': [695], 'hydrazone': [697], 'linkers': [698, 851, 915, 1453, 1839], 'sensitive': [699], 'reductive': [702], 'acidic': [704], 'environment': [705], 'cell': [709, 863, 1404, 1433, 1589, 1601, 1706, 1787, 1980, 1989, 2202, 2461, 2468, 2470, 2832, 3699, 3867, 3918, 3937, 3959, 4318, 4377], '(2Omelyanenko': [710], 'V.': [711, 1265, 1309], 'Gentry': [712], 'Kopeckova': [714], 'P.': [715, 1375, 1379, 1500], 'Kopecek': [716], 'Int.': [718], 'Cancer.': [720], '1998;': [721], '75:': [722], '600-608Crossref': [723], '(93)': [726], 'Scholar,': [728, 755, 782, 832, 1056, 1134, 1498, 2268, 2283, 2296, 2307, 2327, 2342, 3292, 3646, 3756], '3Chan': [729], 'S.Y.': [730], 'Gordon': [731, 1071, 1236, 1325, 1551, 1610, 1674, 1723, 1905, 2561, 2992, 3297, 3825], 'A.N.': [732], 'Coleman': [733], 'R.E.': [734], 'Hall': [735], 'J.B.': [736], 'Finkler': [743], 'N.J.': [744], 'Immunol.': [746, 1489], 'Immunother.': [747, 1490], '2003;': [748, 778, 825, 1049, 1088, 1253, 1691, 1740, 1922, 3285, 3639, 3749, 3842, 4122], '52:': [749], '243-248Crossref': [750], '(54)': [753], '4Di': [756], 'Paolo': [757], 'Willuda': [759], 'Kubetzko': [761], 'S.': [762, 1363, 2081, 2089, 2317], 'Lauffer': [763], 'I.': [764, 838, 1289], 'Tschudi': [765], 'D.': [766, 944, 1200, 1269, 1285, 2272], 'Waibel': [767], 'R.': [768, 807, 834, 1074, 1239, 1277, 1291, 1307, 1677, 1726, 1908, 2083, 3828], 'Pluckthun': [769], 'A.': [770, 790, 2270, 2300, 2313, 2329], 'Stahel': [771], 'Zangemeister-Wittke': [773], 'U.': [774], 'Res.': [777, 841, 897, 998, 1129, 1161, 1347, 1381, 1504, 1573, 1632, 1881, 2302, 2583, 3014, 3319], '9:': [779], '2837-2848PubMed': [780], '5Tolcher': [783], 'A.W.': [784, 890, 1122], 'Ochoa': [785], 'L.': [786, 796, 942, 1198], 'Hammond': [787], 'L.A.': [788], 'Patnaik': [789], 'Edwards': [791], 'T.': [792, 803, 836, 1293, 1485], 'Takimoto': [793], 'Smith': [795], 'de': [797], 'Bono': [798], 'Schwartz': [800], 'G.': [801, 990, 1373, 1873], 'Mays': [802], 'Jonak': [804], 'Z.L.': [805], 'Johnson': [806], 'DeWitte': [808], 'Martino': [810], 'Audette': [812], 'Maes': [814], 'K.': [815, 948, 982, 1066, 1204, 1231, 1328, 1477, 1481, 1554, 1613, 1669, 1718, 1865, 1900, 2564, 2995, 3300, 3820], 'Chari': [816], 'R.V.': [817], 'Lambert': [818, 1516], 'Rowinsky': [820], 'E.K.': [821], '21:': [826, 1050, 2321, 3286, 3640, 3750, 4123], '211-222Crossref': [827], '(174)': [830], '6Hassan': [833], 'Bera': [835], 'Pastan': [837], '2004;': [842, 1162, 1315, 1348, 1382, 1574, 1633, 2094, 2584, 3015, 3320], '10:': [843, 1163, 1349, 1575, 1634, 2585, 3016, 3321], '3937-3942Crossref': [844], '(355)': [847], 'readily': [852, 1596], 'deliver': [853], 'liberate': [855], 'toxin': [859], 'within': [860, 4201, 4263, 4368], 'yet': [865], 'relatively': [867], 'unstable': [868], 'circulation': [870], 'compared': [871, 3354, 3863], 'circulating': [874], 'half-life': [875], '(7Sanderson': [879, 1111], 'R.J.': [880, 1112, 1952, 3664, 3774], 'Hering': [881, 1113], 'M.A.': [882, 1114], 'James': [883, 1115], 'S.F.': [884, 1116], 'Sun': [885, 1117, 1141], 'M.M.': [886, 1118, 1142], 'Doronina': [887, 1079, 1119, 1244, 1335, 1561, 1620, 1682, 1731, 1913, 2571, 3002, 3307, 3833], 'S.O.': [888, 1020, 1080, 1120, 1245, 1336, 1562, 1621, 1683, 1732, 1914, 1936, 2572, 3003, 3256, 3308, 3610, 3648, 3720, 3758, 3834, 4093], 'Siadak': [889, 1121], 'Senter': [891, 1045, 1083, 1123, 1137, 1248, 1341, 1374, 1567, 1626, 1686, 1735, 1917, 1957, 2577, 3008, 3281, 3313, 3635, 3669, 3745, 3779, 3837, 4118], 'P.D.': [892, 1046, 1084, 1124, 1138, 1249, 1297, 1342, 1568, 1627, 1687, 1736, 1918, 1958, 2578, 3009, 3282, 3314, 3636, 3670, 3746, 3780, 3838, 4119], 'Wahl': [893, 1041, 1085, 1125, 1250, 1343, 1569, 1628, 1688, 1737, 1919, 1955, 2579, 3010, 3277, 3315, 3631, 3667, 3741, 3777, 3839, 4114], 'A.F.': [894, 980, 1042, 1086, 1126, 1251, 1344, 1570, 1629, 1689, 1738, 1863, 1920, 1956, 2580, 3011, 3278, 3316, 3632, 3668, 3742, 3778, 3840, 4115], '2005;': [898, 1130], '11:': [899, 1131], '843-852PubMed': [900, 1132], 'Scholar),': [902, 1003, 1169, 1220, 1260, 1319, 1355, 1698], 'premature': [905], 'release.': [907], 'An': [908], 'alternative': [909], 'approach': [910], 'employ': [913], 'ADC': [914, 973, 1422, 1471, 1649, 1701, 1752, 2956, 3363, 3892, 4383], 'protease-cleavable': [917, 1838, 3711], 'dipeptides.': [918], 'combine': [920], 'qualities': [921], 'plasma': [928], 'efficient': [930], 'potentially': [933, 3694], '(8Dubowchik': [937, 1193], 'G.M.': [938, 1194], 'Firestone': [939, 1195], 'Padilla': [941, 1197], 'Willner': [943, 1199], 'Hofstead': [945, 1201], 'S.J.': [946, 952, 1202, 1208], 'Mosure': [947, 1203], 'Knipe': [949, 1205, 1478], 'J.O.': [950, 1206], 'Lasch': [951, 1207], 'Trail': [953, 1209], 'P.A.': [954, 1210], 'Bioconjug.': [955, 1211, 1959, 3671, 3781], 'Chem.': [956, 1212, 1960, 2259, 3672, 3782], '2002;': [957, 999, 1213, 1505, 1882, 2320, 2335, 2350], '13:': [958, 1214], '855-869Crossref': [959, 1215], '(388)': [962, 1218], 'Using': [965, 1789], 'this': [966, 1393], 'strategy,': [967], 'recently': [969], 'described': [970, 1860, 2222, 2427, 2555, 2798, 3717], 'new': [972, 4047], '(9Wahl': [979, 1862], 'Klussman': [981, 1065, 1230, 1327, 1553, 1612, 1668, 1717, 1864, 1899, 2563, 2994, 3299, 3819], 'Thompson': [983, 1866], 'J.D.': [984, 1867, 2806], 'Chen': [985, 1868], 'J.H.': [986, 1869], 'Francisco': [987, 995, 1039, 1157, 1339, 1565, 1624, 1870, 1878, 2575, 3006, 3275, 3311, 3629, 3739, 4112], 'L.V.': [988, 1871], 'Risdon': [989, 1872], 'Chace': [991, 1029, 1067, 1139, 1232, 1331, 1557, 1616, 1670, 1719, 1874, 1901, 2567, 2998, 3265, 3303, 3619, 3729, 3821, 4102], 'D.F.': [992, 1030, 1068, 1140, 1233, 1332, 1558, 1617, 1671, 1720, 1875, 1902, 2568, 2999, 3266, 3304, 3620, 3730, 3822, 4103], 'Siegall': [993, 1037, 1081, 1246, 1337, 1563, 1622, 1684, 1733, 1876, 1915, 2573, 3004, 3273, 3309, 3627, 3737, 3835, 4110], 'J.A.': [996, 1040, 1058, 1158, 1223, 1340, 1566, 1625, 1661, 1710, 1879, 1892, 2576, 3007, 3276, 3312, 3630, 3740, 3812, 4113], '62:': [1000, 1506, 1883], '3736-3742PubMed': [1001, 1884], 'anti-tubulin': [1007], '(MMAE),': [1012], 'cathepsin-cleavable': [1015], 'linker': [1018, 1098, 3713], '(10Doronina': [1019, 3255, 3609, 3719, 4092], 'Toki': [1021, 1075, 1240, 1678, 1727, 1909, 1949, 3257, 3611, 3661, 3721, 3771, 3829, 4094], 'B.E.': [1022, 1076, 1241, 1679, 1728, 1910, 1950, 3258, 3612, 3662, 3722, 3772, 3830, 4095], 'Torgov': [1023, 3259, 3613, 3723, 4096], 'M.Y.': [1024, 3260, 3614, 3724, 4097], 'Mendelsohn': [1025, 1937, 3261, 3615, 3649, 3725, 3759, 4098], 'B.A.': [1026, 1938, 3262, 3616, 3650, 3726, 3760, 4099], 'Cerveny': [1027, 1059, 1145, 1224, 1323, 1549, 1608, 1662, 1711, 1893, 1941, 2559, 2990, 3263, 3295, 3617, 3653, 3727, 3763, 3813, 4100], 'C.G.': [1028, 1060, 1146, 1225, 1324, 1550, 1609, 1663, 1712, 1894, 1942, 2560, 2991, 3264, 3296, 3618, 3654, 3728, 3764, 3814, 4101], 'DeBlanc': [1031, 1073, 1238, 1676, 1725, 1907, 3267, 3621, 3731, 3827, 4104], 'R.L.': [1032, 1305, 3268, 3622, 3732, 4105], 'Gearing': [1033, 3269, 3623, 3733, 4106], 'R.P.': [1034, 3270, 3624, 3734, 4107], 'Bovee': [1035, 1939, 3271, 3625, 3651, 3735, 3761, 4108], 'T.D.': [1036, 1940, 3272, 3626, 3652, 3736, 3762, 4109], 'Meyer': [1043, 1061, 1155, 1226, 1333, 1559, 1618, 1664, 1713, 1895, 1945, 2569, 3000, 3279, 3305, 3633, 3657, 3743, 3767, 3815, 4116], 'D.L.': [1044, 1062, 1156, 1227, 1334, 1560, 1619, 1665, 1714, 1896, 1946, 2570, 3001, 3280, 3306, 3634, 3658, 3744, 3768, 3816, 4117], 'Nat.': [1047, 3283, 3637, 3747, 4120], 'Biotechnol.': [1048, 3284, 3638, 3748, 4121], '778-784Crossref': [1051, 3287, 3641, 3751, 4124], '(892)': [1054, 3290, 3644, 3754, 4127], '11Francisco': [1057], 'Mixan': [1063, 1228, 1329, 1555, 1614, 1666, 1715, 1897, 2565, 2996, 3301, 3817], 'B.J.': [1064, 1229, 1330, 1556, 1615, 1667, 1716, 1898, 2566, 2997, 3302, 3818], 'Rejniak': [1069, 1234, 1672, 1721, 1903, 3823], 'S.X.': [1070, 1150, 1235, 1673, 1722, 1904, 3824], 'K.A.': [1072, 1237, 1326, 1552, 1611, 1675, 1724, 1906, 2562, 2993, 3298, 3826], 'Law': [1077, 1242, 1310, 1680, 1729, 1911, 3831], 'C.L.': [1078, 1243, 1322, 1548, 1607, 1681, 1730, 1912, 2558, 2989, 3294, 3832], 'Blood.': [1087, 1252, 1524, 1690, 1739, 1921, 2334, 3841], '102:': [1089, 1254, 1692, 1741, 1923, 3843], '1458-1465Crossref': [1090, 1255, 1693, 1742, 1924, 3844], '(674)': [1093, 1258, 1696, 1745, 1927, 3847], 'This': [1096, 3174], 'system': [1099], 'shown': [1101], 'be': [1103, 1413], 'stable': [1105], 'vivo': [1110], '12Hamblett': [1135], 'K.J.': [1136], 'Lenox': [1143], 'Kissler': [1147], 'K.M.': [1148], 'Bernhardt': [1149], 'Kopcha': [1151], 'A.K.': [1152], 'Zabinski': [1153, 1953, 3665, 3775], 'R.F.': [1154, 1954, 3666, 3776], '7063-7070Crossref': [1164], '(891)': [1167], 'when': [1171], 'applied': [1172], 'mAbs,': [1175], 'ADCs': [1178, 1810, 1836, 3926, 4068, 4147, 4160, 4188, 4229, 4262, 4276, 4309, 4367, 4417], 'were': [1179, 1531, 1541, 2013, 2033, 2104, 2120, 2136, 2182, 2226, 2241, 2424, 2506, 2532, 2546, 2596, 2620, 2652, 2661, 2724, 2739, 2758, 2778, 2795, 2838, 2930, 2939, 3085, 3109, 3121, 3150, 3336, 3371, 3422, 3435, 3446, 3460, 3483, 3522, 3571, 3714, 3798, 3862, 4063, 4135, 4189, 4270, 4350, 4420], 'selectively': [1180], 'against': [1184, 1458, 1544, 3915, 3934], 'cognate': [1185], 'xenografts': [1191], '(LeY': [1192], '(11Francisco': [1222, 1660, 1709, 1891, 3811], 'TMEFF2': [1261], '(13Afar': [1262], 'D.E.': [1263], 'Bhaskar': [1264], 'Ibsen': [1266], 'Breinberg': [1268], 'Henshall': [1270], 'S.M.': [1271], 'Kench': [1272], 'J.G.': [1273], 'Drobnjak': [1274], 'Powers': [1276, 1284], 'Wong': [1278], 'Evangelista': [1280], 'F.': [1281], "O'Hara": [1282], 'DuBridge': [1286], 'R.B.': [1287], 'Caras': [1288], 'Winter': [1290], 'Anderson': [1292], 'Solvason': [1294], 'N.': [1295], 'Stricker': [1296], 'Cordon-Cardo': [1298], 'Scher': [1300], 'H.I.': [1301], 'Grygiel': [1302], 'Sutherland': [1304], 'Murray': [1306], 'Ramakrishnan': [1308], 'D.A.': [1311], 'Mol.': [1312], 'Ther.': [1314, 2093], '3:': [1316], '921-932PubMed': [1317], 'CD20': [1320], '(14Law': [1321, 1547, 1606, 2557, 2988], '7842-7851Crossref': [1350, 1576, 1635, 2586, 3017, 3322], '(102)': [1353, 1579, 1638, 2589, 3020, 3325], 'EphB2': [1357], '(15Mao': [1358], 'W.': [1359, 2250, 2287], 'Luis': [1360], 'Ross': [1362], 'Silva': [1364], 'Tan': [1366], 'Crowley': [1368], 'Chui': [1370], 'Franz': [1372], 'Koeppen': [1376], 'Polakis': [1378], '64:': [1383], '781-788Crossref': [1384], '(111)': [1387], 'Scholar)).': [1389], 'One': [1390], 'premise': [1391], 'technology': [1396], 'mAb-antigen': [1400, 1429], 'complex': [1401], 'on': [1402, 1428, 1587, 2045, 2457, 2518, 2741, 2840, 2975, 3129, 3583, 3864, 3956, 4278, 4302, 4375], 'will': [1406], 'internalize,': [1407], 'traffic': [1408], 'metabolized': [1414], 'efficacy': [1423], 'therefore': [1424], 'depends': [1425], 'part': [1427], 'at': [1431, 2115, 2122, 2149, 2196, 2404, 2419, 2524, 2694, 2700, 2773, 2786, 2873, 2880, 2889, 2896, 2918, 2925, 3043, 3468, 4081, 4281], 'triggering': [1435], 'subsequent': [1440], 'payload.': [1446], 'Thus,': [1447], 'comprised': [1449], 'different': [1451, 1456], 'mAbs': [1457], 'same': [1460], 'vary': [1463], 'significantly': [1464, 3896], 'their': [1466, 1814], 'utility.': [1467], 'For': [1468, 3929], 'example,': [1469, 3930], 'anti-CD20': [1470, 1537, 1584], 'incorporating': [1472], 'doxorubicin': [1473], '(16Braslawsky': [1474], 'G.R.': [1475, 2346], 'Kadow': [1476], 'McGoff': [1480], 'Edson': [1482], 'Kaneko': [1484], 'Greenfield': [1486], 'R.S.': [1487], '1991;': [1491], '33:': [1492], '367-374Crossref': [1493], '(82)': [1496], '17Sapra': [1499], 'Allen': [1501, 2255], 'T.M.': [1502], '7190-7194PubMed': [1507], 'Scholar)': [1509, 1530, 1886, 1929, 1968, 2357, 3327], 'ricin-A': [1511], '(18Goulet': [1512], 'A.C.': [1513], 'Goldmacher': [1514], 'V.S.': [1515], 'Baron': [1518], 'Roy': [1520], 'D.C.': [1521], 'Kouassi': [1522], '1997;': [1525], '90:': [1526], '2364-2375Crossref': [1527], 'ineffective': [1532], 'as': [1533, 1859, 2221, 2426, 2554, 2797, 3338, 3716, 3964, 4019], 'agents,': [1535], 'whereas': [1536, 1591], 'vcMMAE': [1540], 'CD20+': [1545], 'tumors': [1546], 'Interestingly,': [1582], 'remained': [1586], 'surface,': [1590], 'anti-CD20vc-MMAE': [1593], 'internalized,': [1597], 'rapid': [1600, 1703], 'cycle': [1602], 'arrest': [1603, 1705], 'apoptosis': [1605, 1708], 'Alternatively,': [1641], 'targeting': [1643], 'CD30,': [1644], 'comparable': [1651, 3799], 'binding': [1652, 3801], 'internalization': [1654, 1753, 4054, 4088], 'rates': [1655], 'CD30+': [1657, 1784, 1976, 3803, 3865, 3957, 4060], 'inducing': [1702], 'mitotic': [1704], 'Just': [1748], 'what': [1749], 'governs': [1750], 'optimal': [1751], 'critical': [1756], 'known.': [1763], 'Here': [1764], 'examine': [1766], 'cAC10-drug': [1778, 2417, 3030], 'T-cell': [1785], 'lymphoma': [1786, 2469, 3866], 'lines.': [1788], 'flow': [1790, 2128, 2229, 4149], 'cytometry,': [1791], 'immunofluorescence,': [1792], 'fractionation,': [1794], 'chemical': [1796], 'processing,': [1801], 'demonstrate': [1803, 1828], 'peptide-linked': [1808], 'contingent': [1812], 'upon': [1813], 'lysosome': [1818], 'proteases.': [1825], 'functional': [1830], 'Flow': [1843], 'Cytometry': [1844], 'Antibody': [1846, 2493], 'Antibody-Drug': [1848, 2495], 'Conjugate': [1849, 2496], 'Internalization': [1850], 'Trafficking—The': [1852], 'produced': [1858], 'previously': [1861, 2556, 2799, 3718], 'conjugated': [1888], 'MMAE': [1890, 3178, 3589, 3706, 3883], '(MMAF)': [1934], '(19Doronina': [1935], 'Alley': [1943, 3655, 3765], 'S.C.': [1944, 3656, 3766], 'Oflazoglu': [1947, 3659, 3769], 'Sanderson': [1951, 3663, 3773], '2006;': [1961, 3673, 3783], '17:': [1962, 3674, 3784], '114-124Crossref': [1963, 3675, 3785], '(409)': [1966, 3678, 3788], 'yield': [1970, 3348], 'respectively.': [1974], 'Hodgkin': [1977, 1987, 2459], 'disease': [1978, 1988, 2460], 'L540cy': [1979, 2011, 2027, 2239, 2463, 2688, 3079, 3365, 3872, 4061, 4264, 4370], 'line,': [1981], 'derivative': [1983], 'L540': [1986], 'line': [1990, 2462, 2471, 3938], 'adapted': [1991], 'xenograft': [1993], 'growth,': [1994], 'provided': [1996], 'Dr.': [1998], 'Harald': [1999], 'Stein': [2000], '(Institut': [2001], 'fur': [2002], 'Pathologie,': [2003], 'University': [2004], 'Veinikum': [2006], 'Benjamin': [2007], 'Franklin,': [2008], 'Berlin,': [2009], 'Germany).': [2010], 'grown': [2014], 'RPMI': [2016, 3526], '1640': [2017], 'supplemented': [2018], '20%': [2020], 'heat-inactivated': [2021], 'fetal': [2022], 'calf': [2023], 'sera': [2024], 'antibiotics.': [2026], '(1': [2029, 3537], '×': [2030, 2500, 2691, 2755, 2788, 2835, 2875, 2891, 2920, 3368, 3457, 3538], '106': [2031], 'cells/ml)': [2032, 2693], 'incubated': [2034, 2053, 2114, 2137, 2155, 2187, 2507, 2686, 2759, 2839, 3039, 3086, 3436, 3461, 3499, 3572, 4271, 4301], '2': [2036, 2066, 4207], 'μg/ml': [2037, 2067, 2140, 2158, 2192, 2380, 2383, 2510, 3047, 3089, 3392, 3402, 3554], 'cAC10vc-MMAE,': [2039, 2512], '30': [2043, 2055, 2147, 2402, 2516, 2843], 'min': [2044, 2056, 2148, 2195, 2403, 2517, 2844, 2879, 2895], 'ice,': [2046], 'rinsed': [2047, 2105], 'ice-cold': [2049, 2782], 'then': [2052, 2154, 2931, 3186, 4295], 'presence': [2059, 2705, 2952, 3064, 3096, 3549], '(cross-linking)': [2060], 'absence': [2062, 2707, 3066, 3098, 3551, 4247], '(no': [2063], 'cross-linking)': [2064], 'goat': [2068, 2159, 2441, 2604, 2638], 'anti-human': [2069, 2442, 2605, 3221, 3230, 4074], 'IgG': [2070, 2168, 2606, 2613, 2640, 2647, 3193, 3222, 3231, 4075], '(Jackson': [2071, 2447], 'Immunoresearch,': [2072], 'West': [2073, 3202], 'Grove,': [2074], 'PA)': [2075], '(20Coffey': [2076], 'G.P.': [2077], 'Stefanich': [2078], 'Palmieri': [2080], 'Eckert': [2082], 'Padilla-Eagar': [2084], 'Fielder': [2086], 'P.J.': [2087], 'Pippig': [2088], 'Pharmacol.': [2091], 'Exp.': [2092], '310:': [2095], '896-904Crossref': [2096], '(50)': [2099], 'cold': [2107, 2185, 2535, 2846], 'resuspended': [2109, 2903], 'growth': [2111, 2761, 3463, 3527, 3560], 'media,': [2112], '37': [2116, 2197, 2420, 2525, 2701, 2774, 3469, 4082, 4282, 4355], '°C.': [2117, 2421, 2526, 2775, 2898, 2927, 4083], 'samples': [2119, 2929], 'harvested': [2121, 4136], 'various': [2123], 'times': [2124, 4287], 'processed': [2126, 2425, 3447, 4296], 'cytometry.': [2129], 'detect': [2131, 2175, 3172, 3206], 'surface-bound': [2132, 2203, 4140], '10': [2139, 2157, 2194, 2382, 2855, 2878, 3068, 3380, 3491, 3596], 'mouse': [2141, 2612, 3168, 3555], 'anti-id': [2142, 2219], '4': [2150, 2405, 2881, 2897, 2926, 3466, 3577], '°C,': [2151, 4356], 'washed,': [2152], 'anti-mouse': [2160, 2639, 3192], 'IgG-fluorescein': [2161, 2443], 'isothiocyanate': [2162], 'minimal': [2164, 2609, 2643], 'cross-reactivity': [2165, 2610, 2644], 'human': [2167, 2646], '(Fcγ-specific,': [2169], 'F(ab′)2': [2170], 'fragment;': [2171], 'Jackson': [2172, 3196, 3225], 'Immunoresearch).': [2173, 2448], 'washed': [2183, 2199, 2533, 2780, 3484], 'proteinase': [2189], 'K': [2190], '(5': [2191, 2499, 2754, 2834, 2933, 3456, 3502], '°C),': [2198], 'remove': [2201, 2538], 'antibody,': [2204, 2628, 2634, 3214, 3557], 'treated': [2206, 4070], 'Cytofix/Cytoperm': [2208, 2551], '(BD': [2209], 'Biosciences,': [2210], 'San': [2211, 2398], 'Jose,': [2212], 'CA)': [2213, 2400, 3252], 'prior': [2214, 2407, 3163, 3414, 3427, 3471, 3579, 4078], 'incubation': [2216, 2413, 2599, 3165], 'above.': [2223], 'assessed': [2227, 3562, 4138], 'cytometry': [2230, 4150], 'using': [2231, 2483, 3188, 3218, 4328], 'Becton': [2233], 'Dickinson': [2234], 'FACScan.': [2235], 'In': [2236, 2669, 3074, 3451, 3681], 'experiments,': [2238, 2671, 3076, 3453], 'preincubated': [2242, 4064], '(21Harrison': [2247], 'P.T.': [2248, 2814], 'Davis': [2249], 'Norman': [2251], 'J.C.': [2252], 'Hockaday': [2253], 'A.R.': [2254], 'Biol.': [2258], '1994;': [2260], '269:': [2261], '24396-24402Abstract': [2262], 'Full': [2263], 'Text': [2264], 'PDF': [2265], '22Durrbach': [2269], 'Louvard': [2271], 'Coudrier': [2273], 'Cell': [2276, 3559, 4153], 'Sci.': [2277], '1996;': [2278], '109:': [2279], '457-465Crossref': [2280], '23Brown': [2284], 'B.K.': [2285], 'Song': [2286], 'Traffic.': [2288], '2:': [2290], '414-427Crossref': [2291], '(76)': [2294, 2325], '24Szpaderska': [2297], 'A.M.': [2298], 'Frankfater': [2299], '61:': [2304], '3493-3500PubMed': [2305], '25Booth': [2308], 'J.W.': [2309], 'Kim': [2310], 'M.K.': [2311], 'Jankowski': [2312], 'Schreiber': [2314], 'A.D.': [2315], 'Grinstein': [2316], 'EMBO': [2318], '251-258Crossref': [2322], '26Mueller': [2328], 'Kelly': [2330], 'Strange': [2332], 'P.G.': [2333], '99:': [2336], '785-791Crossref': [2337], '(134)': [2340], '27Sieczkarski': [2343], 'S.B.': [2344], 'Whittaker': [2345], 'Gen.': [2348], 'Virol.': [2349], '83:': [2351], '1535-1545Crossref': [2352], '(401)': [2355], '(10': [2358], 'μm': [2359, 2362, 2365, 2369, 2372, 2391, 2395, 2712, 3069, 3101, 3105, 3375, 3378, 3381, 3385, 3397, 3407], 'colchicine,': [2360], '0.5': [2361, 3377], 'amantadine,': [2363], '0.1': [2364], 'phenylarsine': [2366], 'oxide,': [2367], '20': [2368, 2394, 3100, 3374, 3391, 3396, 3401, 4180], 'clasto-lactacystin-β-lactone,': [2370], '40': [2371], 'cytochalasin': [2373, 2713], 'D,': [2374], '3': [2375, 2698, 2716, 3041, 3104, 3384], 'mm': [2376, 2717, 2853, 2856, 3054, 3057, 3492, 3511, 3514], 'ammonium': [2377, 2718], 'chloride,': [2378], '14': [2379], 'chlorpromazine,': [2381], 'nystatin;': [2384], 'Sigma)': [2385], '(3': [2390], 'CA074-OME': [2392], 'E64d;': [2396], 'Calbiochem,': [2397], 'Diego,': [2399], '°C': [2406, 2702, 3470, 4283], '3-': [2410], '5-h': [2412], 'above': [2428], 'except': [2432], 'detection': [2434, 3215], 'done': [2436], 'staining': [2438, 2623, 2727, 4320, 4362, 4374], 'isothiocyanate-labeled': [2444], 'secondary': [2445, 2633], 'Quantitative': [2449], 'evaluation': [2450], 'expression': [2454], 'anaplastic': [2466], 'large': [2467], '(ALCL)': [2472], 'Karpas-299': [2473, 3870], '(Deutsche': [2474], 'Sammlung': [2475], 'von': [2476], 'Mikroorganism': [2477], 'und': [2478], 'Zellkulturen,': [2479], 'GmbH)': [2480], 'performed': [2482, 3187, 3217], 'QiFiKiT': [2485], 'bead': [2486], 'assay': [2487], '(DAKO,': [2488], 'Carpinteria,': [2489], 'CA).': [2490], 'Immunofluorescence': [2491, 4252], 'Trafficking—L540cy': [2497], '105': [2501, 2692, 2756, 3458], 'cells/ml': [2502], 'regular': [2504], 'medium)': [2505], '1': [2509, 2852, 3412, 4335], 'ice': [2519, 2841, 3117, 4279, 4303], '16': [2522, 4395], 'h': [2523, 2699, 2772, 2924, 3042, 3093, 3413, 3426, 3467, 3506, 3564, 3578, 3942, 4220, 4396], 'After': [2527], 'incubation,': [2529, 4404], 'PBS': [2536], 'unbound': [2539], 'fixed': [2547, 2742], 'permeabilized': [2549], 'stained': [2553, 2653, 4305], 'detected': [2597], 'Alexa': [2601, 2635, 2678, 2764, 2954], 'Fluor': [2602, 2636, 2679, 2765], '488-labeled': [2603, 2766], '(H+L)': [2607, 2641], '(Molecular': [2614, 2648, 2683, 2735], 'Probes,': [2615], 'Eugene,': [2616], 'OR).': [2617], 'Lysosomal': [2618, 2720], 'compartments': [2619, 2651, 2723], 'visualized': [2621, 2725, 4327], 'Lamp-1': [2625, 4389], '(mouse': [2626], 'CD107a': [2627], 'BD': [2629], 'Biosciences)': [2630], '568-conjugated': [2637], 'Probes).': [2649, 2736], 'Nuclear': [2650], '4′,6′-diamidino-2-phenylindole': [2655], '(Roche': [2656], 'Applied': [2657], 'Science).': [2658], 'Fluorescence': [2659, 2737], 'images': [2660, 2738], 'acquired': [2662], 'Leitz': [2665], 'Orthoplan': [2666], 'epifluorescence': [2667], 'microscope.': [2668, 2750], '488': [2680], 'reactive': [2681], 'dye': [2682, 3253, 3575], 'Probes)': [2684], '(2': [2690, 3035, 3053, 3510], '200': [2695], 'ng/ml': [2696], '(40': [2711], 'D': [2714], 'chloride).': [2719], 'nuclear': [2722], 'LysoTracker': [2729, 4345, 4400], 'Hoescht': [2731], 'dyes,': [2733], 'respectively': [2734], 'taken': [2740], 'Carl': [2746], 'Zeiss': [2747], 'Axiovert': [2748], '200M': [2749], 'Fractionation—L540cy': [2752], 'cells)': [2757, 2837, 3459], 'medium': [2762, 3464, 3528], '(8': [2768, 3367], 'μg/ml)': [2769, 3503], '18': [2771, 2923, 3092], 'harvested,': [2779], 'pelleted': [2785], '500': [2787], 'g': [2789, 2876, 2892, 2921], '5': [2791, 3046, 3088, 4209], 'min.': [2792], 'Lysosome-enriched': [2793], '(Axis-Shield,': [2800], 'Oslo,': [2801], 'Norway': [2802], 'Ref.': [2804], '28Castle': [2805], 'Coligan': [2807], 'J.E.': [2808], 'Dunn': [2809], 'B.M.': [2810], 'Speicher': [2811], 'D.W.': [2812], 'Wingfield': [2813], 'Current': [2815], 'Protocols': [2816], 'Protein': [2818], 'Science.': [2819], '1.': [2820], 'John': [2821], 'Wiley': [2822], '&': [2823], 'Sons,': [2824], 'Inc.,': [2825], 'New': [2826], 'York2004:': [2827], '4.2.1-4.2.57Google': [2828], 'Briefly,': [2830], 'pellets': [2833], '107': [2836], 'homogenization': [2847, 2905], 'buffer': [2848, 2906, 3052, 3126, 3489, 3509], '(0.25': [2849], 'm': [2850, 3487], 'sucrose,': [2851], 'EDTA,': [2854], 'HEPES,': [2857, 3493], 'pH': [2858, 3060, 3494, 3517], '7.4)': [2859], 'gently': [2861], 'Dounce': [2862], 'homogenized': [2863], 'break': [2865], 'open': [2866], 'homogenate': [2870], 'spun': [2872], '3000': [2874], 'supernatant': [2884], 'collected': [2886], 'centrifuged': [2888], '17,000': [2890], '15': [2894], 'pellet': [2901], 'mixed': [2908, 3122], '60%': [2910], 'OptiPrep': [2911], '(Axis-Shield;': [2912], 'final': [2913], 'concentration,': [2914], '20%)': [2915], 'before': [2916], 'centrifugation': [2917], '208,000': [2919], 'fractionated': [2932], 'drops/fraction),': [2934], '25': [2937, 3406, 3441], 'assayed': [2940], 'marker,': [2944], 'β-galactosidase': [2945], '(metabolism': [2947], '4-methylumbelliferyl-β-d-galactopyranoside;': [2949], 'Sigma),': [2950], 'Fluor-labeled': [2955], 'fluorimetry': [2958], '(Fusion-HT;': [2959], 'Packard': [2960], 'Instruments,': [2961], 'Meridien,': [2962], 'CT),': [2963], 'loss': [2966], 'associated': [2969], 'heavy': [2971, 3208], 'light': [2973, 3210], 'chains': [2974, 3211], 'frame': [2978], 'Western': [2980, 3023], 'blot': [2981], 'analyses': [2982], 'anti-MMAE': [2985, 3556], 'SG2.15': [2986, 3169], 'Blot': [3024], 'Analyses—To': [3025], 'evaluate': [3026, 4050], 'units/ml;': [3036], 'Calbiochem)': [3037], '37°C': [3044], 'dithiothreitol,': [3055, 3512], '50': [3056, 3513], 'sodium': [3058, 3515], 'acetate,': [3059, 3516], '5.0)': [3061], 'E64d': [3070, 3102], 'inhibitor.': [3073], 'Karpas': [3077, 3454], 'pooled': [3080], 'lysosome-enriched': [3081], '(numbers': [3083], '10-19)': [3084], 'CA074-OME.': [3106], 'reactions': [3108], 'stopped': [3110], 'quick': [3112], 'freezing': [3113], 'dry': [3116, 3155], 'bath.': [3118], 'digests': [3120], 'Novex': [3124], 'sample': [3125], '(Invitrogen),': [3127], 'run': [3128], '4-20%': [3130], 'Tris-Gly': [3131], '4-12%': [3133], 'Bis-Tris': [3134], 'gradient': [3135], 'gels': [3136], '(Invitrogen)': [3137], 'under': [3138], 'reducing': [3139], 'conditions,': [3140], 'transferred': [3142], 'onto': [3143], 'polyvinylidene': [3144], 'difluoride': [3145], 'membranes': [3146, 3149], '(Invitrogen).': [3147], '2%': [3153], 'nonfat': [3154], 'milk': [3156], 'PBST': [3158], '(PBS+': [3159], '0.1%': [3160], 'Tween': [3161], '20)': [3162], 'recognizes': [3176], 'MMAF': [3180, 3591, 3692, 3708], '(data': [3181], 'shown).': [3183], 'Detection': [3184], 'horseradish': [3190, 3219, 3228], 'peroxidase-goat': [3191, 3220, 3229], '(Fcγ': [3194, 3223], 'specific,': [3195], 'Immunoresearch)': [3197, 3226], 'followed': [3198, 3238], 'ECL': [3200], '(SuperSignal': [3201], 'Pico;': [3203], 'Pierce).': [3204], 'specific;': [3224], '(κ-specific;': [3232], 'Southern': [3233], 'Biotech,': [3234], 'Birmingham,': [3235], 'AL),': [3236], 'respectively,': [3237], 'ECL.': [3240], 'Cytotoxicity': [3241], 'Assay—Cell': [3242], 'viability': [3243, 3353], 'measured': [3245], 'Alamar': [3247, 3567], 'Blue': [3248], '(BIOSOURCE': [3249], 'International,': [3250], 'Camarillo,': [3251], 'reduction': [3254, 3351], '14Law': [3293], 'Celltiter-Glo': [3330, 3438], '(Promega,': [3331], 'Madison,': [3332], 'WI).': [3333], 'results': [3335], 'reported': [3337, 3793], 'IC50': [3340, 3932], 'values,': [3341], 'concentration': [3343], 'compound': [3345], 'needed': [3346], '50%': [3350], 'untreated': [3356], '(control': [3358], '=': [3359], '100%).': [3360], 'inhibit': [3362, 3604], 'metabolism,': [3364], '103': [3369], 'cells/well)': [3370], 'pretreated': [3372], 'E64d,': [3376], 'CA074-OME,': [3379], 'calpeptin': [3382], '(Calbiochem),': [3383, 3395, 3400], 'N-acetyl-Leu-Leu-Nle-CHO': [3386], '(calpain': [3387], 'inhibitor': [3388], 'I;': [3389], 'Calbiochem),': [3390], 'pepstatin': [3393], 'A': [3394], 'p-aminoethylbenzenesulfonyl': [3398], 'fluoride': [3399], 'aprotinin': [3403], '(Sigma),': [3404], 'cystamine': [3408], 'dihydrochloride': [3409], '(Sigma)': [3410], 'cAC10vc-MMAE.': [3419], 'cultures': [3421, 3532], 'maintained': [3423, 4212], '96': [3425, 3563, 3941], 'Celltiter-Glo.': [3432], 'reagent': [3439], 'min,': [3442], 'dishes': [3445], 'luminescent': [3449], 'readout.': [3450], 'harvesting': [3474], 'generate': [3478], 'fractions.': [3480], '0.25': [3486], 'sucrose': [3488], 'containing': [3490, 3709], '7.2.': [3495], 'Each': [3496], 'fraction': [3497], '24': [3505], 'reaction': [3508], '5.0).': [3518], 'Afterward,': [3519], 'diluted': [3523], '300-fold': [3524], 'added': [3530], 'CD30-negative': [3534, 3809, 3936], 'Ramos': [3535, 3939], '104': [3539], 'cells/well;': [3540], 'Type': [3542], 'Culture': [3543], 'Collection,': [3544], 'Manassas,': [3545], 'VA)': [3546], '2.5': [3553], 'SG3.190.': [3558], 'later': [3565], 'Blue.': [3568], 'fluorescence': [3581], 'measurement': [3582], 'Fusion': [3585], 'HT': [3586], 'plate': [3587], 'reader.': [3588], 'belong': [3592], 'dolastatin': [3595], 'family': [3597], 'anti-mitotic': [3601], 'tubulin': [3605], 'polymerization': [3606], '(Fig.': [3607, 4151, 4170, 4195, 4221, 4250, 4266, 4310, 4390, 4401], '1)': [3608], '19Doronina': [3647, 3757], 'contrast': [3682], 'charged,': [3686], 'carboxylic': [3687], 'acid': [3688], 'terminus': [3689], 'limit': [3695], 'passive': [3696], 'transit': [3697], 'through': [3698], 'membranes.': [3700], 'vc': [3712], 'We': [3791], 'have': [3792], 'cAC10-vcMMAE': [3797], 'lacked': [3806], 'activities': [3851, 3951], 'lines': [3868], 'including': [3869], '(Table': [3873, 3948], '1).': [3874], 'Comparison': [3875], 'showed': [3879, 4316], 'cell-permeable': [3882], '50-200-fold': [3885], 'than': [3888, 3899, 3903], 'MMAF.': [3889], 'As': [3890], 'however,': [3893], '(IC50': [3901], '<': [3902, 3907, 3976, 3984, 3993, 4001, 4010, 4029, 4034, 4039], '0.11': [3904], 'nm,': [3905], 'p': [3906, 4028, 4033, 4038], '0.001).': [3908], 'Neither': [3909], 'exhibited': [3912], 'appreciable': [3913], 'antigen-negative': [3917], 'lines,': [3919], 'demonstrating': [3920], 'potency': [3923], 'these': [3925], 'antigen-dependent.': [3928], 'value': [3933], 'continuous': [3943], 'exposure': [3944], '>75': [3946], 'nm': [3947], '1).TABLE': [3949], '1Cytotoxic': [3950], 'linesCell': [3960], 'lineTypeCD30aCD30': [3961], 'expressed': [3963, 4018], 'number': [3966, 4021], 'molecules': [3969, 4024], 'per': [3971, 4026], 'cell.MMAEMMAFcAC10vc-EcAC10vc-FKarpasALCL': [3972], '(T-cell)290,6760.52': [3973], '±': [3974, 3980, 3982, 3988, 3991, 3997, 3999, 4005, 4008, 4014], '0.29bp': [3975], '0.005': [3977, 3985, 4011, 4030], 'MMAF.101': [3979], '120.11': [3981], '0.016bp': [3983], 'MMAF.0.05': [3987], '0.005L540cyHD': [3989], '(T-cell)587,5111.25': [3990], '0.81cp': [3992], '0.001': [3994, 4002, 4035, 4040], 'MMAF.65.6': [3996], '14.30.32': [3998], '0.032dp': [4000], 'cAC10vc-F.0.11': [4004], '0.035RamosBurkitt': [4006], 'lymphoma00.039': [4007], '0.02bp': [4009], 'MMAF.58': [4013], '10>75>75a': [4015], 'cell.b': [4027], 'MMAF.c': [4032], 'MMAF.d': [4037], 'cAC10vc-F.': [4042], 'Open': [4043], 'table': [4044], 'tab': [4048], 'vehicle': [4072], 'cross-linking': [4077, 4249], 'culture': [4080], 'Cross-linked': [4084], 'exhibit': [4086], 'increased': [4087, 4167, 4230], 'cellular': [4090], 'clearance': [4091], 'At': [4130, 4354], 'appointed': [4131], 'times,': [4132], '2).': [4152], 'decreased': [4161], 'sharply': [4162], 'time,': [4164], 'coincident': [4165], '2),': [4171], 'they': [4174], 'kinetics.': [4178], 'By': [4179], 'h,': [4181, 4210], '∼60%': [4190], 'initial': [4193], '2A).': [4196], 'Intracellular': [4197], 'rose': [4199], 'quickly': [4200], 'hour,': [4204], 'peaked': [4205], 'between': [4206], 'lower': [4213], 'steady': [4215], 'up': [4217], '48': [4219], '2B).': [4222, 4251], 'Cross-linking': [4223], '∼3-fold': [4241], 'over': [4242], 'observed': [4244], 'microscopy': [4253], 'localize': [4257], '3).': [4267], 'either': [4277], 'stated': [4286], 'imaged': [4289], 'immediately': [4290], 'fixed,': [4292], 'permeabilized,': [4293], 'immunofluorescence.': [4298], '3,': [4311, 4338, 4391, 4402], 'top': [4312, 4339], 'panels,': [4313, 4340, 4347], 'green': [4314], 'signal)': [4315, 4342, 4349], 'diffuse,': [4317], 'surface-associated': [4319], 'no': [4322], 'evidence': [4323], 'internalization.': [4325], 'Lysosomes,': [4326], 'lysosome-associated': [4332], 'membrane': [4333], 'protein': [4334], '(Lamp-1;': [4336], 'Fig.': [4337], 'red': [4341, 4348], '(bottom': [4346], 'distinct': [4351], 'punctate.': [4353], 'there': [4357], 'capping': [4359], 'punctate': [4361], 'reduced': [4373], 'surface.': [4378], 'signals': [4384], 'co-localized': [4385], 'those': [4387], 'arrows,': [4392], 'yellow': [4393, 4405], 'signal,': [4394, 4406], 'incubation)': [4397], '3-h': [4403], 'Merged,': [4407], 'data': [4409], 'shown),': [4411], 'transported': [4421], 'l': [4424]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2115292116', 'counts_by_year': [{'year': 2024, 'cited_by_count': 12}, {'year': 2023, 'cited_by_count': 12}, {'year': 2022, 'cited_by_count': 11}, {'year': 2021, 'cited_by_count': 16}, {'year': 2020, 'cited_by_count': 10}, {'year': 2019, 'cited_by_count': 19}, {'year': 2018, 'cited_by_count': 19}, {'year': 2017, 'cited_by_count': 25}, {'year': 2016, 'cited_by_count': 17}, {'year': 2015, 'cited_by_count': 25}, {'year': 2014, 'cited_by_count': 18}, {'year': 2013, 'cited_by_count': 25}, {'year': 2012, 'cited_by_count': 23}], 'updated_date': '2024-12-20T10:58:12.202544', 'created_date': '2016-06-24'}
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