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经单克隆抗体和补体治疗后存活的伯基特淋巴瘤细胞间的抗原异质性

Antigenic heterogeneity among Burkitt's lymphoma cells surviving treatment with monoclonal antibody and complement.

作者信息

De Fabritiis P, Bregni M, Lipton J, Reynolds C, Nadler L, Ritz J, Bast R C

出版信息

Leuk Res. 1986;10(1):35-42. doi: 10.1016/0145-2126(86)90103-7.

Abstract

Selective removal of malignant cells from human bone marrow is one requirement for autologous bone marrow transplantation. In earlier studies treatment with multiple monoclonal antibodies and C' was more effective than treatment with individual reagents in eliminating clonogenic Burkitt's lymphoma cells from a twenty-fold excess of human bone marrow. To explore possible mechanisms underlying the additive or synergistic effects observed with multiple reagents, clones of malignant cells that have survived treatment with antibody and C' have now been isolated at limiting dilution. Marked heterogeneity has been observed in binding of different monoclonal antibodies and in resistance to C'-dependent lysis among these different clones. Phenotypic traits were stable for at least two weeks in culture. Clones that survived treatment with the J5 anti-CALLA antibody and C' exhibited a relative decrease in CALLA expression but did not exhibit an increased susceptibility to lysis by anti-CALLA and C'. No selective decrease in gp-26 or B1 was observed in clones treated with J2 or anti-B1. A correlation between CALLA and gp-26 expression was observed in clones treated with J2 and anti-B1, but no clear correlation was observed between antigen expression and susceptibility to C'-dependent lysis. In this model system, escape from C' dependent cytotoxicity does not appear related to the existence of phenotypically stable C' resistant variants within the tumor cell population.

摘要

从人骨髓中选择性去除恶性细胞是自体骨髓移植的一项要求。在早期研究中,用多种单克隆抗体和补体(C')进行治疗在从二十倍过量的人骨髓中清除克隆性伯基特淋巴瘤细胞方面比用单个试剂治疗更有效。为了探索用多种试剂观察到的相加或协同效应的潜在机制,现在已通过有限稀释法分离出了在用抗体和补体(C')处理后存活的恶性细胞克隆。在这些不同克隆中,观察到不同单克隆抗体的结合以及对补体(C')依赖性裂解的抗性存在明显的异质性。表型特征在培养中至少两周保持稳定。在用J5抗CALLA抗体和补体(C')处理后存活的克隆中,CALLA表达相对降低,但对抗CALLA和补体(C')介导的裂解的敏感性并未增加。在用J2或抗B1处理的克隆中,未观察到gp-26或B1的选择性降低。在用J2和抗B1处理的克隆中观察到CALLA和gp-26表达之间存在相关性,但在抗原表达与对补体(C')依赖性裂解的敏感性之间未观察到明显的相关性。在这个模型系统中,逃避补体(C')依赖性细胞毒性似乎与肿瘤细胞群体中表型稳定的补体(C')抗性变体的存在无关。

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