Immunotherapy of ovarian cancer with t-cell receptor Vbeta-specific, ex vivo-expanded cytotoxic T lymphocytes (Meeting abstract).

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Immunotherapy of ovarian cancer with t-cell receptor Vbeta-specific, ex vivo-expanded cytotoxic T lymphocytes (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 37:A3339 1996. Unique Identifier : AIDSLINE ICDB/97633339
Oshidari F; Muniappan A; Freedman R; Lebkowski J; Talib S; Applied Immune Sciences Incorporated, Santa Clara, CA 95054

Abstract: Recognition of tumor-associated antigen in the context of MHC, and subsequent activation of T-lymphocytes, are mediated by the alphabeta heterodimer of the T-cell receptor (TCR). The specificity of a TCR is determined by variable regions of alpha and beta chains (Valpha and Vbeta) and the third complimentary determining region (CDR3). The presence of a limited and dominant Vbeta repertoire in tumor infiltrating lymphocytes (TIL) and tumor associated lymphocytes (TAL) might reflect the clonal expansion of those T-cells with specific TCR recognizing a specific tumor antigen. Adoptive immunotherapy with a population of TCR-specific TIL/TAL might be a more efficient option. To this end, we have sought to characterize, isolate, and ex vivo-expand TCR-specific CD8+ T lymphocytes from PBL, TAL, and TIL of ovarian cancer patients. Vbeta usage and clonal expansion of T-cell population were determined by a multiprobe RNase protection assay and a highly sensitive PCR-based method that determines the CDR3 size patterns. Vbeta3 and Vbeta13 were the dominant oligoclonal repertoires in CD8+ TIL of an HLA-A2+ ovarian cancer patient. We isolated and expanded Vbeta3+ and Vbeta13+ T-cells from PBL of this patient 6 weeks post TIL therapy, using AIS MicroCELLectors containing immobilized Vbeta monoclonal antibodies. Vbeta3+ and Vbeta13+ CD8+ enriched cultures (greater than 95%) showed high levels of cytotoxic activity (50-90% specific lysis and significant levels of IFNgamma and GM-CSF secretion) against HLA-A2+ allogeneic tumor target cells. Our data suggest that it is possible to isolate and expand Vbeta-specific CD8+ cytotoxic T-cells ex vivo. Such TCR-specific T-cell population can enhance the effectiveness of adoptive immunotherapy of various cancers.

Keywords: CD8-Positive T-Lymphocytes/IMMUNOLOGY Female Human *Immunotherapy, Adoptive Lymphocyte Transformation Lymphocytes, Tumor-Infiltrating/*IMMUNOLOGY/TRANSPLANTATION Ovarian Neoplasms/IMMUNOLOGY/*THERAPY Receptors, Antigen, T-Cell/*METABOLISM T-Lymphocytes, Cytotoxic/IMMUNOLOGY ABSTRACT
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M9731541

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