AUTOLOGOUS THERAPEUTIC TUMOR VACCINE + IFN GAMMA IN OVARIAN CANCER

这项研究的长期目标是开发有效的卵巢癌特异性肿瘤免疫治疗方法。许多临床前研究的结果表明，通过使用由共表达MHC抗原和B7.1共刺激因子的自体肿瘤细胞组成的治疗性疫苗，在体内诱导抗肿瘤T细胞激活是可能的。以前的研究结果表明，在某些情况下，卵巢肿瘤浸润性淋巴细胞可能代表了体内被激活的淋巴细胞群体，MHC参与了激活过程。在体内，树突状细胞或其他专业性APC可能参与了T细胞的激活。我们已经在卵巢癌患者的腹膜腔内发现了树突状细胞，但这些细胞大部分不表达CD80。因此，我们提出了一项试点临床试验，以确定IP注射感染ALVAC-hB7.1的新鲜分离的EOC细胞是否可行，以及IP注射也表达B7.1的自体肿瘤细胞是否导致体内肿瘤特异性免疫的激活。患者将接受3个剂量水平的ALVAC-B7.1感染细胞的治疗。ALVAC-B7.1感染的肿瘤细胞将只在第一周接种。在ALVAC-B7.1感染的肿瘤细胞治疗前的第2周和第3周，先注射两剂重组干扰素-g。3周的治疗相当于一个疗程。在没有进展的情况下，如果有肿瘤细胞可用，将给予进一步的疫苗和重组干扰素疗程。

The long-term goal of this study is to develop effective specific tumor immune therapy for ovarian cancer. Results from a number of preclinical studies suggest that it is possible to induce anti-tumor T-cell activation in vivo by the use of a therapeutic vaccine composed of autologous tumor cells that co-express MHC antigens and the B7.1 costimulatory factor. Results of previous studies suggest that ovarian tumor infiltrating lymphocytes may in some instances represent a population of lymphocytes that have been activated in vivo, and that the MHC is involved in the activation process. It is probable that dendritic cells or other professional APC's contribute to activation of T-cells in vivo. We have identified dendritic cells in the peritoneal cavity of EOC patients, but for the most part these cells do not express CD80. We have therefore proposed a pilot clinical trial to determine whether IP injection of freshly isolated EOC cells infected with the ALVAC-hB7.1 is feasible, and whether the IP injection of autologous tumor cells that also express B7.1 results in activation of tumor specific immunity in vivo by standard methods of evaluation. Patients will be treated at 3 dose levels of ALVAC-B7.1 infected cells. ALVAC-B7.1 infected tumor cells only will be given the first week. Two doses of rIFN-g will precede treatment with ALVAC-B7.1 infected tumor cells in weeks 2 and 3. The 3 week treatment equals a single course of treatment. In the absence of progression and if tumor cells are available, further courses of vaccine and rIFN will be administered.