Cytotoxic T-lymphocyte immunotherapy for ovarian cancer: a pilot study.
Cytotoxic T-lymphocyte immunotherapy for ovarian cancer: a pilot study.
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DOI：
10.1097/cji.0b013e318243f213
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Robinson W
中科院分区：
文献类型：
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作者：
Wright SE;Rewers-Felkins KA;Quinlin IS;Phillips CA;Townsend M;Philip R;Dobrzanski MJ;Lockwood-Cooke PR;Robinson W
目的是评估腹腔内（IP）输注肿瘤特异性细胞毒性T淋巴细胞（CTL）治疗复发性卵巢癌的毒性和可行性，并确定重复周期的CTL产生和输注是否可测量地增加宿主的卵巢癌免疫应答。在这项研究中，7例局限于腹膜腔的复发性卵巢癌受试者接受了多达4个周期，每个周期从白细胞分离术开始，用于收集前体淋巴细胞，这些前体淋巴细胞在体外用MUC 1刺激，MUC 1是卵巢癌细胞中常见的肿瘤特异性抗原。通过IP输注将每个周期产生的新CTL重新引入宿主。免疫参数（杀伤细胞，细胞因子的生产，记忆T淋巴细胞和自然杀伤（NK）细胞）进行了研究。还评价了毒性、CA-125和存活数据。肿瘤标志物CA-125在免疫治疗的第一个月后无统计学显著降低。但之后，它又上升了。杀伤细胞，细胞因子的产生和记忆T淋巴细胞增加后的第一个周期的刺激，但稳定或减少之后。NK细胞百分比与其他免疫参数呈负相关。中位生存期为11.5个月。1例受试者自2000年12月以来无疾病。超过一个周期的多个周期的T细胞刺激随后过继性T细胞输注可能不会增强体内免疫应答。
The objective was to evaluate the toxicity and feasibility of intraperitoneal (IP) infusion of tumor-specific cytotoxic T-lymphocytes (CTL) as therapy for recurrent ovarian cancer, and to determine if repetitive cycles of CTL generation and infusion measurably increases the host’s ovarian cancer immune response. In this study, seven subjects with recurrent ovarian cancer confined to the peritoneal cavity underwent up to 4 cycles, each cycle beginning with a leukapheresis for collection of precursor lymphocytes, which were stimulated in vitro with MUC1, a tumor-specific antigen found commonly in ovarian cancer cells. The resulting new CTL for each cycle were re-introduced into the host via IP infusion. Immunological parameters (killer cells, cytokine production, memory T-lymphocytes and natural killer (NK) cells) were studied. Toxicity, CA-125, and survival data were also evaluated. The tumor marker CA-125 was non statistically significantly reduced after the first month of immunotherapy. However, after that, it rose. Killer cells, cytokine production and memory T-lymphocytes increased after the first cycle of stimulation, but plateaued or reduced thereafter. The percent of NK cells inversely correlated with other immune parameters. Median survival was 11.5 months. One subject is free of disease since December, 2000. Multiple cycles, beyond one cycle, of T-cell stimulation followed by adoptive T cell infusion, may not enhance the in vivo immune response.