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使用同基因单克隆抗体治疗小鼠肉瘤

Therapy of a murine sarcoma using syngeneic monoclonal antibody.

作者信息

Kennel S J, Lankford T, Flynn K M

出版信息

Cancer Res. 1983 Jun;43(6):2843-8.

PMID:6850596
Abstract

Syngeneic monoclonal antibodies (MoAb) to Moloney sarcoma cells (MSC) were produced by fusion of spleen cells from MSC regressor mice to myeloma SP2/0. MoAb 244-19A, an immunoglobulin G2b, bound to MSC cells and did not bind to two other sarcomas (K-BALB and Ha2), a carcinoma (Line 1), a fibroblast (A31) or a fibroblast infected with C-type virus (A31-Moloney leukemia virus). In contrast, MoAb 271-1A bound to the MSC and Ha2 sarcoma and line 1 carcinoma as well as to the normal and infected fibroblast cultures. Antibodies were tested for therapeutic effect using three schedules of antibody injection. Injection i.p. of ascites fluid containing 244-19A MoAb given on Days-1, 0, and +1 relative to tumor cell injection increased life span significantly over that of control animals given injections (P3, immunoglobulin G, or MoAb 271-1A) and produced some seven of 19, one of five, and one of five long-term survivors in three separate experiments. Antibody given to animals with established tumors (4 days after implantation) also prolonged life span significantly and produced three of nine long-term survivors. Antibody given to animals with very large tumor burdens (10 days after implantation) did not prolong life span significantly. Optimal dose, schedule, and mechanism studies concerning this therapy are in progress.

摘要

通过将莫洛尼肉瘤细胞(MSC)消退小鼠的脾细胞与骨髓瘤SP2/0融合,制备了针对莫洛尼肉瘤细胞的同基因单克隆抗体(MoAb)。免疫球蛋白G2b型单克隆抗体244 - 19A与MSC细胞结合,而不与另外两种肉瘤(K - BALB和Ha2)、一种癌(Line 1)、一种成纤维细胞(A31)或感染C型病毒的成纤维细胞(A31 - 莫洛尼白血病病毒)结合结合A31)结合。相比之下,单克隆抗体271 - 1A与MSC、Ha2肉瘤、Line 1癌以及正常和成纤维细胞培养物结合。使用三种抗体注射方案测试了抗体的治疗效果。相对于肿瘤细胞注射,在第 - 1、0和 + 1天腹腔注射含244 - 19A单克隆抗体的腹水,与接受注射的对照动物相比,显著延长了生存期(P3、免疫球蛋白G或单克隆抗体271 - 1A),并且在三个独立实验中分别产生了19只中的7只、5只中的1只和5只中的1只长期存活者。给已形成肿瘤的动物(植入后4天)注射抗体也显著延长了生存期,并产生了9只中的3只长期存活者。给肿瘤负荷非常大的动物(植入后10天)注射抗体并未显著延长生存期。关于这种治疗的最佳剂量、方案和机制研究正在进行中。

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