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: 6113552
• 负责人: VERNON K. SONDAK
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6113552
• 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. Furthermaor, 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，人类肉瘤表达可能被 T 细胞识别的肿瘤相关抗原。 尽管有这些观察结果，但很明显，这些抗原的弱点和/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，并且这种反应可能对治疗有用。 我们建议利用源自广泛临床前研究的方法生成疫苗引发的 T 细胞，用于 IV 期肉瘤患者的免疫治疗。 这些研究表明，来自肿瘤疫苗接种引发的淋巴结的淋巴细胞含有 T 细胞，这些 T 细胞在体外激活后可以针对免疫原性较差的肿瘤产生特异性抗肿瘤反应。 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在治疗上更有效，并且可以克服 T 细胞的全身免疫抑制。 本文提出的研究将对引发针对肉瘤相关肿瘤抗原的 T 细胞反应的要求产生重要的见解，并使我们能够研究肿瘤诱导的 T 细胞信号转导分子 TCR- 的抑制是否存在于肉瘤患者中。