ADOPTIVE CELL THERAPY OF SOFT TISSUE SARCOMAS USING AUTOLOGOUS TUMOR VACCINATION

使用自体肿瘤疫苗接种软组织肉瘤的过继细胞疗法

• 批准号: 6274786
• 负责人: VERNON K. SONDAK
• 金额: $ 2.15万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6274786
• 关键词: T cell receptor; T lymphocyte; autologous transplantation; clinical research; colony stimulating factor; human subject; human therapy evaluation; immunosuppression; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; passive immunization; sarcoma; transfection; tumor antigens

It has recently been demonstrated that human sarcomas express tumor- associated antigens potentially capable of being recognized by T cells. Despite these observations, it is evident that the weakness of these antigens and/or the presence of tumor-induced suppression results in an ineffective immune response in cancer patients. We hypothesize that the immune response to sarcoma can be modulated to elicit T cells reactivity, and that this response may be useful for therapy. We propose to generate vaccine-primed T cells for the immunotherapy of stage IV sarcoma patients utilizing methods derived from extensive preclinical studies. These studies have demonstraed that lympohocytes from lymph nodes primed by tumor vaccination harbor T cells which can develop specific antitumor reactivity against poorly immunogenic tumors after in vitro activation. Furthermore, animal data suggests that using vaccines composed of tumor cells transfected with the GM-CSF gene are more therapeutically efficacious and may overcome systemic immunosuppression of T cells. The studies proposed herein will yield important insights into the requirements for eliciting T cell responses against sarcoma-associated tumor antigens, and will allow us to study whether tumor-induced suppression of the T cell signal transduction molecule TCR- is present in sarcoma patients.

最近已经证明人类肉瘤表达肿瘤- 相关抗原可能被 T 细胞识别。 尽管有这些观察结果，但很明显这些方法的弱点 抗原和/或肿瘤诱导的抑制的存在导致 癌症患者的免疫反应无效。 我们假设 可以调节对肉瘤的免疫反应以引发 T 细胞 反应性，并且这种反应可能对治疗有用。 我们 提议生成疫苗引发的 T 细胞用于免疫治疗 IV 期肉瘤患者采用广泛的方法 临床前研究。 这些研究表明淋巴细胞 来自经过肿瘤疫苗接种激发的淋巴结含有 T 细胞，这些 T 细胞可以 针对免疫原性差的肿瘤产生特异性抗肿瘤反应 体外激活后。 此外，动物数据表明，使用 由转染 GM-CSF 基因的肿瘤细胞组成的疫苗 更有效的治疗并且可以克服全身性的 T 细胞的免疫抑制。 本文提出的研究将产生 关于引发 T 细胞反应的要求的重要见解 对抗肉瘤相关肿瘤抗原，并使我们能够研究 肿瘤是否诱导T细胞信号转导抑制 分子 TCR- 存在于肉瘤患者体内。