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.

最近已经证明了人类肉瘤表达肿瘤 相关的抗原可能能够被T细胞识别。 尽管有这些观察，但很明显这些弱点 抗原和/或存在肿瘤诱导的抑制导致 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起T细胞 反应性，这种反应可能对治疗有用。 我们 提议生成疫苗生化的T细胞以进行免疫疗法 IV期肉瘤患者利用广泛的方法得出的方法 临床前研究。 这些研究证明了淋巴细胞 来自肿瘤疫苗接种引发的淋巴结，可以 针对不良免疫原性肿瘤发展特定的抗肿瘤反应性 体外激活后。 此外，动物数据表明使用 由GM-CSF基因转染的肿瘤细胞组成的疫苗是 更有效地治疗，可能会克服系统性 T细胞的免疫抑制。 本文提出的研究将产生 对引发T细胞反应的要求的重要见解 反对与肉瘤相关的肿瘤抗原，并将允许我们研究 肿瘤诱导的T细胞信号转导抑制是否抑制 分子TCR-存在于肉瘤患者中。