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T Cells Demonstrated in a Mouse Model of Prostate Cancer1
* Division of Hematology and Oncology and
Bone Marrow Transplantation and Cell Therapy Program, Department of Medicine,
Anatomic Pathology, and
Program in Molecular and Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294
In contrast to Ag-specific 
β T cells, 
T cells can kill malignantly transformed cells in a manner that does not require the recognition of tumor-specific Ags. Although such observations have contributed to the emerging view that T cells provide protective innate immunosurveillance against certain malignancies, particularly those of epithelial origin, they also provide a rationale for developing novel clinical approaches to exploit the innate antitumor properties of T cells for the treatment of cancer. Using TRAMP, a transgenic mouse model of prostate cancer, proof-of-concept studies were performed to first establish that T cells can indeed provide protective immunosurveillance against spontaneously arising mouse prostate cancer. TRAMP mice, which predictably develop prostate adenocarcinoma, were backcrossed with T cell-deficient mice (TCR–/– mice) yielding TRAMP x TCR–/– mice, a proportion of which developed more extensive disease compared with control TRAMP mice. By extension, these findings were then used as a rationale for developing an adoptive immunotherapy model for treating prostate cancer. Using TRAMP-C2 cells derived from TRAMP mice (C57BL/6 genetic background), disease was first established in otherwise healthy wild-type C57BL/6 mice. In models of localized and disseminated disease, tumor-bearing mice treated i.v. with supraphysiological numbers of syngeneic T cells (C57BL/6-derived) developed measurably less disease compared with untreated mice. Disease-bearing mice treated i.v. with T cells also displayed superior survival compared with untreated mice. These findings provide a biological rationale for clinical trials designed to adoptively transfer ex vivo expanded autologous T cells for the treatment of prostate cancer.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work is supported in part by a Congressionally Directed Medical Research Programs Award DAMD17-03-1-0265 from the U.S. Department of Defense.
2 Address correspondence and reprint requests to Dr. Richard D. Lopez, BMI Program, 541 Tinsley Harrison Tower, The University of Alabama at Birmingham, 1900 University Boulevard, Birmingham, AL 35294. E-mail address: Richard.Lopez{at}ccc.UAB.edu
3 Abbreviation used in this paper: GU, genitourinary.
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