| Abstract: |
Effective vaccination against cancer, either for prophylaxis or therapy, has been an elusive goal for years. Cytokine gene therapy offers a novel approach to generate immunogenic tumor cell vaccines. To examine the feasibility of cytokine gene transfer into human renal cancer (RC) cells, we introduced the cDNAs for human interleukin-2 (IL-2) or interferon-γ (IFN-γ) into various RC cell lines with retroviral vectors. Using the NIH3T3 amplification assay, no replication competent retroviral particles were detectable in cell culture supernatants taken from gene-modified RC cell lines. Efficient expression of both lymphokines was achieved. Depending on the cell line and the vector construct used, lymphokine gene-modified human RC cell lines released 4 to 29 units/106 cells of IL-2, or up to 10 units/106 cells of IFN-γ within 48 h. Fluorescence-activated cell sorter analysis of SK-RC-29 cells releasing IFN-γ showed increased expression of major histocompatibility complex class I antigen-microglobulin, and ICAM-1, as well as induction of major histocompatibility complex class II antigen expression [human leukocyte antigen(HLA)-DR, -DP], but no changes in these cell surface markers were observed with SK-RC-29 cells releasing IL-2. Following in vitro 7-irradiation with 5,000 or 10,000 rad, growth of lymphokine gene-modified RC cells was abrogated, but their capability to release lymphokine and express lymphokine-induced antigenic determinants, such as HLA-DR, was retained. Tumor formation by the human RC cell line SK-RC-29 in BALB/c nude mice was not affected by IFN-γ secretion, but was inhibited by in vivo release of IL-2 from s.c. injected tumor cells. These studies demonstrate the feasibility of retroviral mediated lymphokine-gene transfer into human RC cells and suggest a means for generating autologous or HLA-matched allogeneic tumor cell vaccines for the treatment of patients with renal cell carcinoma. © 1992, American Association for Cancer Research. All rights reserved. |
| Keywords: |
controlled study; human tissue; human cell; antigen expression; phenotype; animal; mice; cell survival; interleukin 2; gene expression; tumor cells, cultured; transfection; mice, inbred balb c; kidney carcinoma; kidney neoplasms; dose-response relationship, radiation; carcinogenesis; gene transfer; genetic vectors; dna; antigens, neoplasm; gamma interferon; carcinoma, renal cell; mice, nude; gene therapy; transplantation, heterologous; beta 2 microglobulin; virus replication; kidney cancer; tumor vaccine; major histocompatibility complex; intercellular adhesion molecule 1; complementary dna; retrovirus; retroviridae; interleukin-2; major histocompatibility antigen class 1; gamma rays; interferon type ii; fluorescence activated cell sorter; human; male; priority journal; article; lymphokines; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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