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MAGE-1-specific Precursor Cytotoxic T-Lymphocytes Present among Tumor-infiltrating Lymphocytes from a Patient with Breast Cancer: Characterization and Antigen-specific Activation¹

Departments of Pathology [J. F. T.] and Surgery [C. O., H. K. L., K. J. W.], Duke University Medical Center, Durham, North Carolina 27710; Virogenetics, Inc., Troy, New York 12180 [J. T., E. P.]; and Applied Immune Sciences, Inc., Santa Clara, California 95054 [F. O., S. T.]

A potential target for development of tumor-specific immunotherapeutic strategies is the MAGE-1 gene. We have utilized a recently developed recombinant canarypox (ALVAC) virus vector containing the MAGE-1 gene (vCP235) to activate CTLs from a breast cancer patient bearing a MAGE-1⁺ tumor. Tumor-infiltrating lymphocytes (TILs) obtained from the tumor of a patient were stimulated in vitro with irradiated autologous peripheral blood mononuclear cells acutely infected with the vCP235 construct. These TILs preferentially expanded approximately 6-fold over a 16-day culture period and specifically recognized an allogeneic transformed B-cell line acutely infected with a vaccinia-MAGE-1 recombinant targeting vector (vP1188) in the context of HLA-A2 and/or B7. TCR Vß analysis of in vitro expanded T cells by a quantitative multiprobe RNase protection assay revealed preferential expansion of TCR Vß6.3 and Vß6.4. In addition, homologous T-cell receptor ß CDR3 joining sequences were found in the in vitro stimulated cultures. These results suggest that tumor antigen-specific, MHC-restricted CTLs may be derived from precursor CTLs present in TILs obtained from patients with MAGE-1⁺ tumors by in vitro stimulation with recombinant avipox MAGE-1 virus-infected autologous cells. Collectively, these findings provide a rationale for tumor-associated antigen-based immunization as a means of activating precursor CTLs residing in patients with tumors expressing defined tumor-associated antigens such as MAGE-1.

¹ This work was supported by NIH Awards 1-RO1-CA58005 and 1-P50-CA68438 (Duke University SPORE in Breast Cancer) and NIH Training Grant 5-T32-AI07392 (J. F. T.).

² To whom requests for reprints should be addressed, at Department of Surgery, Box 2926, Duke University Medical Center, Durham, NC 27710-2926.

Received 10/ 4/95. Accepted 11/14/95.

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