PuSH - Publication Server of Helmholtz Zentrum München: Influence of CD80 Interleukin2, and Interleukin-7 Expression in Human Renal Cell Carcinoma on the Expression, Function, and Survival of Tumor-Specific CTLs.

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Frankenberger, B. ; Pohla, H. ; Nößner, E. ; Willimsky, G.* ; Papier, B. ; Pezzutto, A.* ; Kopp, J.* ; Oberneder, R. ; Blankenstein, T. ; Schendel, D.J.

Influence of CD80 Interleukin2, and Interleukin-7 Expression in Human Renal Cell Carcinoma on the Expression, Function, and Survival of Tumor-Specific CTLs.

Clin. Cancer Res. 11, 1733-1742 (2005)

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Purpose: A renal cell carcinoma (RCC) line, RCC-26, has been identified as a suitable candidate for development of an allogeneic tumor cell vaccine based on its expression of a variety of tumor-associated antigens (TAA). To improve immunogenicity, RCC-26 cells were genetically engineered to express CD80 alone or in combination with interleukin (IL)-2 or IL-7. The effect of these modifications on proliferation, function, and survival of autologous and allogeneic tumor-specific CTLs was assessed. Experimental Design: RCC-26 sublines expressing different transgenes were tested for their capacity to reactivate cytokine secretion and cytotoxicity in autologous tumor-infiltrating lymphocytes, to improve proliferation and survival of tumor-associated T cells present in autologous peripheral blood, and to induce tumor-associated responses in naive allogeneic lymphocytes. The expression of several common TAA was quantitated in the RCC-26 sublines using reverse transcription-PCR to identify surrogate markers for immune monitoring in clinical trials. Results: Gene-modified RCC-26 cells showed enhanced immunogenicity. CD80 expression was necessary to induce RCC-associated CTL in blood of healthy allogeneic donors. It also improved proliferation of autologous effector-memory T cells. Further enhancement was achieved with IL-2 through induction of the antiapoptosis protein Bcl-x_L. The candidate vaccine lines overexpressed several common TAA that are suitable markers for immune monitoring. Conclusions: RCC-26 cells coexpressing CD80 and cytokine transgenes display improved immunogenic characteristics, supporting their use as allogeneic tumor cell vaccines for HLA-A2-matched patients with metastatic RCC.

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