Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen Journal Article


Authors: Chekmasova, A. A.; Rao, T. D. ; Nikhamin, Y.; Park, K. J.; Levine, D. A.; Spriggs, D. R.; Brentjens, R. J.
Article Title: Successful eradication of established peritoneal ovarian tumors in SCID-Beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen
Abstract: 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. ©2010 AACR.
Keywords: unclassified drug; human cell; nonhuman; t lymphocyte; ovarian neoplasms; t-lymphocytes; animal cell; mouse; animals; mice; peritoneal neoplasms; animal experiment; animal model; membrane proteins; antineoplastic activity; cytotoxicity; in vitro study; mice, scid; tumor cells, cultured; xenograft model antitumor assays; tumor antigen; ovary tumor; tumor cell line; tumor cell; retrovirus vector; adoptive transfer; ca-125 antigen; cytokine release; antigen presenting cell; immunotherapy, adoptive; scid mouse; muc16 antigen; cytotoxicity tests, immunologic
Journal Title: Clinical Cancer Research
Volume: 16
Issue: 14
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2010-07-15
Start Page: 3594
End Page: 3606
Language: English
DOI: 10.1158/1078-0432.ccr-10-0192
PUBMED: 20628030
PROVIDER: scopus
PMCID: PMC2907178
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric
Citation Impact
MSK Authors
  1. Renier J Brentjens
    270 Brentjens
  2. Douglas A Levine
    369 Levine
  3. Kay Jung Park
    248 Park
  4. David R Spriggs
    324 Spriggs