ADOPTIVE CELL THERAPY OF SOFT TISSUE SARCOMAS USING AUTOLOGOUS TUMOR VACCINATION

最近有研究表明，人类肉瘤表达的肿瘤相关抗原可能能够被免疫系统识别。然而，这些抗原的薄弱和/或肿瘤诱导抑制的存在导致肉瘤患者的免疫反应无效。我们建议利用来自广泛的临床前研究的方法，为IV期肉瘤患者的免疫治疗产生疫苗准备的T细胞。这些研究表明，从肿瘤疫苗接种部位引流的淋巴结细胞(淋巴细胞)中含有T细胞，经体外激活后，T细胞可对免疫原性差的肿瘤产生特异性抗肿瘤反应。本文提出的研究将对激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。

It has recently been shown that human sarcomas express tumor-associated antigens potentially capable of being recognized by the immune system. However, the weakness of these antigens and/or the presence of tumor-induced suppression results in an ineffective immune response in sarcoma patients. 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 demonstrated that lymph node cells (lymphocytes) from lymph nodes draining the site of a tumor vaccination harbor T cells which can develop specific antitumor reactivity against poorly immunogenic tumors after in vitro activation. The studies proposed herein will yield important insights into the requirements for eliciting T cell responses against sarcoma-associated tumor antigens.