Clinical Cancer Research 11: 1733-1742 (2005-01-01)

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

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

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

Type: Article

PubMed: 15755994
Official URL:
MDC Repository: