INTERLEUKIN-2 SECRETION BY TRANSDUCED AND UNSELECTED BDL-2 LYMPHOMA RESULTS IN INCREASED SURVIVAL IN MICE WITH PREVIOUSLY ESTABLISHED DISSEMINATED DISEASE

The transfer and expression of cytokine genes into malignant cells to provide a more effective tumor response has shown promise. The majorit y of murine models in which tumor vaccination strategies have been tes ted have utilized selected and expanded clones of tumor cells, which i s impractical clinically. In a model of murine B lineage lymphoma (BDL -2), we compared the effectiveness of tumor vaccines composed of a) a BDL-2 clone established by G-418 resistance following transduction wit h the LIL2SN retrovirus and screened for maximal IL-2 secretion, b) a syngeneic fibroblast line transduced with LIL2SN and screened for G-41 8 resistance and IL-2 expression, which was co-injected with the paren tal line, and c) a heterogeneous (unselected) population of BDL-2 cell s transduced with the MFG/IL2 virus, reported to provide enhanced expr ession of cytokine genes and minimize the need for selection. Testing of splenocytes derived from vaccinated animals reveals that injections of BDL-2 expressing IL-2 results in an increased capacity of splenocy tes to kill BDL-2 in vitro, compared to vaccination of BDL-2 alone or in combination with IL-2 secreting fibroblasts. We show that a vaccine composed of MFG/IL2 transduced, unselected BDL-2 cells is equivalent or superior to a clone derived from LIL2SN transduction in prolonging survival of animals wish previously established tumor. These studies p rovide evidence that transduction of tumor with MFG based vectors with out in vitro selection leads to expression of high levels of IL-2 and can impact the survival of animals with disseminated tumor.