THERAPY OF HUMAN B-CELL LYMPHOMA BEARING SCID MICE IS MORE EFFECTIVE WITH ANTI-CD19-SAPORIN AND ANTI-CD38-SAPORIN IMMUNOTOXINS USED IN COMBINATION THAN WITH EITHER IMMUNOTOXIN USED ALONE
THERAPY OF HUMAN B-CELL LYMPHOMA BEARING SCID MICE IS MORE EFFECTIVE WITH ANTI-CD19-SAPORIN AND ANTI-CD38-SAPORIN IMMUNOTOXINS USED IN COMBINATION THAN WITH EITHER IMMUNOTOXIN USED ALONE
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DOI：
10.1002/ijc.2910620318
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发表时间：
1995-07-28
影响因子：
6.4
通讯作者：
FLAVELL, SU
中科院分区：
文献类型：
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作者：
FLAVELL, DJ;BOEHM, DA;FLAVELL, SU
CD19(+) CD38(+) 人伯基特淋巴瘤细胞系 Ramos 在静脉注射 (i.v) 到严重联合免疫缺陷 (SCID) 小鼠体内时会急剧生长，在 33-42 天内杀死 100% 的动物，并导致疾病广泛传播。静脉注射后 7 天开始治疗与假手术对照组相比，注射 3 剂抗 CD19 免疫毒素（IT；BU12-SAPORIN）或抗 CD38 IT（OKT10-SAPORIN）的 Ramos 细胞可显着延长生存期；抗CD38 IT可最大程度地延长存活时间，但所有接受治疗的动物最终都死于疾病。当两种 IT 以同等剂量水平联合使用时，治疗效果比单一 IT 治疗显着改善，20% 的动物无病生存 300 天。当抗CD38 IT与抗CD19抗体联合使用时，与单独使用抗CD38 IT相比，治疗效果没有改善。然而，当抗CD19 IT与CD38抗体联合使用时，与单独使用抗CD19 IT获得的生存相比，生存期随之显着延长，尽管这不如两种IT联合使用时获得的生存期那么显着，并且仅与单独使用OKT10抗体获得的生存期一样好。 CD19 和 CD38 在绝大多数 B 细胞淋巴瘤和常见急性淋巴细胞白血病细胞的表面表达，我们的研究结果为针对这些靶分子的这些疾病的联合免疫毒素试验提供了合理的理由。 (C) 1995 Wiley-Liss, Inc.
The CD19(+) CD38(+) human Burkitt's lymphoma cell line Ramos grows aggressively when injected intravenously (i.v.) into severe combined immunodeficient (SCID) mice, killing 100% of animals within a 33-42 day period with widely disseminated disease. Treatment commencing 7 days after i.v. injection of Ramos cells, with 3 doses of an anti-CD19 immunotoxin (IT; BU12-SAPORIN) or an anti-CD38 IT (OKT10-SAPORIN) led to a significant prolongation of survival compared with sham-treated controls; the anti-CD38 IT gave the greatest prolongation of survival, but all treated animals eventually succumbed to disease. When both ITs were used in combination at equivalent dose levels, the therapeutic outcome was significantly improved over that obtained for single IT therapy, with 20% of animals surviving disease-free to 300 days. When anti-CD38 IT was given in combination with anti-CD19 antibody there was no therapeutic improvement over anti-CD38 IT used alone. However, when anti-CD19 IT was given in combination with CD38 antibody, a significant prolongation of survival ensued over that obtained with anti-CD19 IT alone, though this was not as significantly pronounced as that obtained when both ITs were used in combination and was only as good as the survival obtained with OKT10 antibody used alone. CD19 and CD38 are expressed on the surface of the vast majority of B-cell lymphoma and common acute lymphoblastic leukaemia cells, and our findings provide a sound rationale for a combination immunotoxin trial in these diseases directed against both these target molecules. (C) 1995 Wiley-Liss, Inc.