Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes: modulation of recognition through retroviral transduction of tumor cells with interleukin 2 complementary DNA and exogenous alpha interferon treatment.
Two cytotoxic effector cell populations were isolated from a patient with renal cell carcinoma. The tumor-infiltrating lymphocytes comprised a population of highly specific, major histocompatibility complex-restricted, cytotoxic T lymphocytes (CTL). An autologous non-major histocompatibility complex-restricted lymphokine-activated killer (LAK) cell population was generated by culturing the peripheral blood lymphocytes with high doses of recombinant interleukin 2 (rIL-2). The capacity of these two effector cell types to lyse cytokine-modulated autologous tumor cells was compared in vitro. A complementary DNA for rIL-2 was introduced into the tumor cells by retroviral transduction, and tumor cells secreting low doses of rIL-2 were isolated. The CTL recognition of these tumor cells was enhanced, compared to unmodified tumor cells, whereas LAK cell recognition was unchanged or slightly reduced. Pretreatment of tumor cells with exogenous alpha interferon led to an up-regulation of some major histocompatibility complex class I molecules and to slightly better recognition by the CTL; little effect on LAK cell recognition was observed. CTL were found to be 50-150-fold more effective than LAK cells in lysing autologous tumor cell lines or clones modulated with both rIL-2 and alpha interferon. The assessment of a patient's cytotoxic immune capacity directed against genetically modified autologous tumor cells in vitro provides important insight for cytokine-mediated gene therapy of cancer.
Schendel
D J
DJ
Institut für Immunologie, Ludwig-Maximilians-Universität München, Germany.
Gansbacher
B
B
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D015316:Genetic Therapy; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins