Human T cells targeted with anti-T3 cross-linked to antitumor antibody prevent tumor growth in nude mice.
Human T cells targeted with anti-T3 cross-linked to antitumor antibody prevent tumor growth in nude mice.
复制标题
人类 T 细胞以与抗肿瘤抗体交联的抗 T3 为靶标，可防止裸鼠体内的肿瘤生长。
DOI：
10.4049/jimmunol.138.11.4018
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发表时间：
1987
影响因子：
4.4
通讯作者：
D. Segal
中科院分区：
文献类型：
--
作者：
J. A. Titus;M. A. Garrido;T. Hecht;D. Winkler;J. Wunderlich;D. Segal
当人外周血T细胞与抗肿瘤抗体交叉连接的抗T3抗体靶向时，测试了其在裸鼠体内防止肿瘤生长的能力。将LS174T人结肠腺癌细胞与315F6(抗肿瘤单抗Fab)包被的抗T3(Fab)包被的人外周血(PBL)混合，接种于裸鼠皮下。效靶比(E：T)为7.0：1和2.1：1时，肿瘤生长被完全抑制，抗体包被的PBL在0.7：1时部分抑制肿瘤生长，而未包被的PBL不能抑制肿瘤生长。当抗肿瘤物质与抗T3抗体发生物理交叉连接时，就会发生T细胞介导的抗肿瘤生长保护作用。无论是未连接的抗T3和抗肿瘤抗体的混合物，还是与抗肿瘤抗体交叉连接的抗人MHC I类抗体，都不能阻止肿瘤的生长。体外细胞毒作用完全由T8+细胞介导，效应细胞短暂暴露于IL-2可增强肿瘤中和作用，而体内肿瘤中和作用由T4+和T8+细胞共同介导，且不受IL-2刺激。我们认为，当人T细胞与适当的抗体异种聚集体作用时，可在低E：T比下特异性地抑制肿瘤生长，体内介导肿瘤中和作用的细胞可能与体外介导的细胞毒作用不同。
Human peripheral blood T cells were tested for the ability to prevent tumor growth in nude mice when targeted with anti-T3 cross-linked to antitumor antibodies. LS174T human colon adenocarcinoma cells were mixed with human PBL coated either with anti-T3 (Fab) cross-linked to 315F6 (Fab) (an antitumor monoclonal antibody) or with no antibody, and were injected subcutaneously into nude mice. Tumor growth was totally inhibited at effector to target (E:T) ratios of 7.0:1 and 2.1:1, and was partially inhibited at 0.7:1 with antibody-coated PBL, but was not inhibited by uncoated PBL. T cell-mediated protection against tumor growth occurred when an antitumor was physically cross-linked to anti-T3. Neither a mixture of unlinked anti-T3 and antitumor antibodies nor anti-human MHC class I cross-linked to antitumor antibody prevented tumor growth. Whereas in vitro cytotoxicity was mediated exclusively by T8+ cells and was augmented by brief exposure of effector cells to IL 2, tumor neutralization in vivo was mediated by both T4+ and T8+ cells and was not significantly stimulated by prior exposure of the cells to IL 2. We conclude that human T cells, when targeted with appropriate antibody heteroaggregates, can specifically inhibit tumor growth at low E:T ratios, and that cells mediating tumor neutralization in vivo may differ from those mediating cytotoxicity in vitro.