期刊
CLINICAL CANCER RESEARCH
卷 16, 期 14, 页码 3594-3606出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-10-0192
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资金
- Damon Runyon Clinical Investigator Award
- Memorial Sloan-Kettering Cancer Center
- Annual Terry Fox Run for Cancer Research (New York, NY)
- Commonwealth Cancer Foundation for Research
- Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center
- Geoffrey Beene Cancer Foundation
- Bocina Cancer Research Fund
- [CA138738-01]
- [PO1 CA052477]
Purpose: Most patients diagnosed with ovarian cancer will ultimately die from their disease. For this reason, novel approaches to the treatment of this malignancy are needed. Adoptive transfer of a patient's own T cells, genetically modified ex vivo through the introduction of a gene encoding a chimeric antigen receptor (CAR) targeted to a tumor-associated antigen, is a novel approach to the treatment of ovarian cancer. Experimental Design: We have generated several CARs targeted to the retained extracellular domain of MUC16, termed MUC-CD, an antigen expressed on most ovarian carcinomas. We investigate the in vitro biology of human T cells retrovirally transduced to express these CARs by coculture assays on artificial antigen-presenting cells as well as by cytotoxicity and cytokine release assays using the human MUC-CD+ ovarian tumor cell lines and primary patient tumor cells. Further, we assess the in vivo antitumor efficacy of MUC-CD-targeted T cells in SCID-Beige mice bearing peritoneal human MUC-CD+ tumor cell lines. Results: CAR-modified, MUC-CD-targeted T cells exhibited efficient MUC-CD-specific cytolytic activity against both human ovarian cell and primary ovarian carcinoma cells in vitro. Furthermore, expanded MUC-CD-targeted T cells infused through either i.p. injection or i.v. infusion into SCID-Beige mice bearing orthotopic human MUC-CD+ ovarian carcinoma tumors either delayed progression or fully eradicated disease. Conclusion: These promising preclinical studies justify further investigation of MUC-CD-targeted T cells as a potential therapeutic approach for patients with high-risk MUC16(+) ovarian carcinomas. Clin Cancer Res; 16(14); 3594-606. (C) 2010 AACR.
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