Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen.
| Autor: | Chekmasova AA; Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA., Rao TD, Nikhamin Y, Park KJ, Levine DA, Spriggs DR, Brentjens RJ |
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| Jazyk: | angličtina |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2010 Jul 15; Vol. 16 (14), pp. 3594-606. Date of Electronic Publication: 2010 Jul 13. |
| DOI: | 10.1158/1078-0432.CCR-10-0192 |
| Abstrakt: | 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. (Copyright 2010 AACR.) |
| Databáze: | MEDLINE |
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