Lymphokine Combination Vectors: A New Tool for Tumor Vaccination in Leukemias/Lymphomas

Abstract

Previously, we have shown that CMS5, a fibrosarcoma, could be induced to secrete lymphokines into the immediate surroundings of the tumor cells following transduction with the interleukin-2 (IL-2) or mouse interferon gamma (IFN-gamma) gene, resulting in a potent antitumor immune response [1, 2]. To explore this system in detail an appropriate animal model, analogous to human tumors which are essentially nonimmunogenic, is required. Since CMS5 is immunogenic and generates a cellular immune response it is not by itself ideal for this purpose. On the other hand, the murine B cell lymphoma 38C13, produced in a C3H/eB mouse depleted of T-cells is weakly immunogenic and expresses an idiotype which essentially constitutes a tumor specific marker. This idiotype has been studied in detail and used in immunotherapeutic models to induce antitumor respones [3–5]. While both humoral and cellular immune responses are important in vivo for resistance to tumor growth, in the 38C13 system the cellular antitumor immune response has been quite suboptimal [6].We will use these genetically modified malignant B-lymphocytes, which we have transduced with lymphokine genes using retroviral gene transfer, to generate specific cytotoxic T-cells in vitro and a cellular antitumor response in vivo. Our findings in the CMS5 system provide a rationale for the hypothesis that lymphokine gene transfer may be successful in enhancing the host’s antitumor response to 38C13.