CELLULAR MECHANISMS IN TUMOR-SPECIFIC IMMUNITY

这项调查的目的是继续努力派生和 体外和体内长期检测其生物学特性 培养、筛选和克隆肿瘤特异性T细胞系。 已经完成的实验给出了这样的信心，即 可提高对化学诱导的小鼠的肿瘤特异性 肉瘤。这些线路可以维持足够长的时间，并且 在足够高的数量上进行广泛的生物学研究，并且可以 在体内检测对肿瘤生长的保护能力 潜在的免疫治疗模式。 到目前为止，已经有50多个抗肿瘤细胞系被衍生和测试，根据 对最初提出的协议。 在此期间，还分离了更多克隆的T细胞系 肿瘤特异性局部保护。推动力一直是更多地依赖于 克隆的过继保护和DTH活性高于体外 细胞毒性试验与以前使用的一样。事实证明，它很难扩展 有效寿命超过50天，不损失特定的杀戮或克隆人死亡。 造成这种情况的原因尚不清楚；已经延长的线路 最多200天都显示出细胞遗传学变化，这表明它们 自发地改变了。 在体内观察克隆系的特异性保护活性 这笔赠款的第一年已经确定。数据现在正在被 准备出版。简而言之，如果特定的细胞系是 注射前与肿瘤混合，如果肿瘤处于早期腹水中 形成并注射细胞，或者如果细胞直接注射 进入肿瘤，就提供了保护。没有任何保护措施可以证明 由其他途径给药的细胞。 在下一阶段，将集中力量提供 初步实验似乎产生了辅助性T细胞系 表型，具有肿瘤特异性活性，由D.T.H.(Lb)证明

The aims of this investigation are to continue efforts to derive and to examine in vitro and in vivo the biological properties of long-term cultured, selected, and cloned tumor-specific T-cell lines. Experiments already completed give confidence that T-cell lines which bear tumor specificity can be raised against chemically induced murine sarcomas. These lines can be sustained for sufficiently long periods and in sufficiently high numbers for a wide range of biological studies and can be tested for the capacity to protect against tumor growth in vivo in potential immunotherapeutic models. To date over 50 antitumor cell lines have been derived and tested according to the protocols proposed originally. During this period, additional cloned T-cell lines have been isolated with tumor-specific partial protection. The thrust has been to rely more upon adoptive protection and DTH activity of the clones than upon in vitro cytotoxicity testing as previously used. It has proven difficult to extend active life beyond 50 days without loss of specific kill or clone death. The reasons for this are not understood; the lines which have been extended up to 200 days have all shown cytogenetic alteration, suggesting that they have spontaneously transformed. In vivo specific protective activity of the cloned lines observed during the first year of this grant has been confirmed. The data are now being prepared for publication. Briefly, if the specific cell lines are either mixed with the tumor before injection, if the tumor is in early ascites form and the cells are injected ip., or if the cells are injected directly into the tumor, protection is afforded. No protection can be demonstrated by cells administered by other routes. During the next period, intensive efforts will be focused upon providing preliminary experiments which appear to yield T-cell lines of helper phenotype, with tumor-specific activity demonstrated by D.T.H. (LB)