CELLULAR MECHANISMS IN TUMOR-SPECIFIC IMMUNITY

肿瘤特异性免疫的细胞机制

• 批准号: 3164156
• 负责人: RICHARD T SMITH
• 金额: $ 8.16万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1986-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3164156
• 关键词: B lymphocyte; Bacillus Calmette Guerin vaccine; Retroviridae; T lymphocyte; cellular immunity; disease /disorder model; fibrosarcoma; host neoplasm interaction; immunochemistry; immunotoxicity; neoplasm /cancer genetics; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; osteosarcoma; tumor antigens

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)

这项调查的目的是继续努力， 在体外和体内检查长期的生物学特性 培养、选择和克隆肿瘤特异性T细胞系。 已经完成的实验使人们相信， 可以提高针对化学诱导的鼠的肿瘤特异性 肉瘤 这些线可以维持足够长的时间， 对于广泛的生物学研究来说， 在体内测试保护免受肿瘤生长的能力， 潜在的免疫模型。 到目前为止，已经衍生出超过50种抗肿瘤细胞系，并根据 最初提出的协议。 在此期间，已经分离了另外的克隆T细胞系， 肿瘤特异性部分保护。 推动力更多地依赖于 过继保护和DTH活性的克隆比在体外 细胞毒性试验，如先前所用。 事实证明， 有效寿命超过50天，没有特定杀伤或克隆死亡的损失。 其原因尚不清楚;延长的线路 长达200天都显示出细胞遗传学改变，这表明它们 已经自发地转化了。 在体外培养期间观察到的克隆系的体内特异性保护活性 第一年的赠款已经确定。 数据现在正在 准备出版。 简单地说，如果特定的细胞系是 如果肿瘤在早期腹水中， 形成并将细胞腹膜内注射，或者直接注射细胞 进入肿瘤，提供保护。 无法证明有任何保护 通过其他途径给予细胞。 在下一个时期，将集中努力， 初步实验似乎产生了辅助T细胞系 表型，具有通过D.T.H.证明的肿瘤特异性活性。 （LB）