Influence of CD80, interleukin-2, and interleukin-7 expression in human renal cell carcinoma on the expansion, function, and survival of tumor-specific CTLs

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Item Type:	Article
Title:	Influence of CD80, interleukin-2, and interleukin-7 expression in human renal cell carcinoma on the expansion, function, and survival of tumor-specific CTLs
Creators Name:	Frankenberger, B., Pohla, H., Noessner, E., Willimsky, G., Papier, B., Pezzutto, A., Kopp, J., Oberneder, R., Blankenstein, T. and Schendel, D.J.
Abstract:	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.
Keywords:	CD80 Antigens, Cancer Vaccines, Cell Proliferation, Cell Survival, Cultured Tumor Cells, Cytokines, Cytotoxic T-Lymphocytes, Gene Expression Profiling, HLA-A2 Antigen, Interleukin-2, Interleukin-7, Kidney Neoplasms, Neoplasm Antigens, Neoplasm Metastasis, Renal Cell Carcinoma, Reverse Transcriptase Polymerase Chain Reaction, Transgenes
Source:	Clinical Cancer Research
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Volume:	11
Page Range:	1733-1742
Date:	1 January 2005
Official Publication:	https://doi.org/10.1158/1078-0432.CCR-04-1883
PubMed:	View item in PubMed

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