Symposium: Cellular Immunity and the Immunotherapy of Cancer: Major Histocompatibility Complex/Human Leukocyte Antigen and Tumors: PDF OnlyPorgador Angel; Tzehoval, Esther; Vadai, Ezra; Feldman, Michael; Eisenbach, LeaJournal of Immunotherapy with Emphasis on Tumor Immunology: October 1993 - p 191-201 Buy Abstract Summary We have comparatively analyzed the immune mechanisms induced by and the immunotherapeutic potentials of a highly metastatic clone of the Lewis lung carcinoma, D122, transduced with the interleukin-2 (IL-2), IL-6, or interferon-7 (IFN-γ) genes. All of the D122 cytokine gene-transduced cells induced antitumor CD8+ cytotoxic T lymphocytes (CTLs), as can be judged from in vivo depletion of CD8+ cells and in vitro CTL assays. In vivo depletion of CD4+ cells did not affect the malignant phenotypes of the different D122 gene-modified cells, but in vivo depletion of natural killer (NK) cells resulted in increased malignancy of both D122 cells and D122 gene-modified cells. In accordance with the effects of in vivo NK depletion, D122 as well as D122 derivative cells were sensitive to lysis by polyinosinic-polycytidylic acid (poly I:C)-induced activity. We discuss the immune responses generated by the different D122 gene-modified cells in view of their in vivo behavior in syngeneic and nude mice. We also performed comparative analysis of the capacity of vaccinations with irradiated D122 gene-modified cells to cure established micrometastases of parental D122 cells in tumor-operated mice. Vaccinations with D122-IL-2 or -IL-6 secretors did not generate a significant effect. Also, vaccinations with D122-IFN-γ cells, which showed increased major histocompatibility complex class I expression but did not secrete detectable levels of IFN-γ, did not cure established micrometastases. Only vaccination with D122- IFN-γ high secretors efficiently cured postoperated mice carrying established micrometastases. We discuss the relevance of these results to the application of immunotherapy via cytokine gene therapy of human malignancy. © Lippincott-Raven Publishers.