Adenoviral Interleukin-2 Gene Transfer into P815 Tumor Cells Abrogates Tumorigenicity and Induces Antitumoral Immunity in Mice

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Abstract
The murine mastocytoma cell line P815 was used as a model to evaluate the effect on its tumorigenic capacity following interleukin-2 (IL-2) gene transfer into the tumor cells using a replication-defective adenovirus vector. The data show that P815 cells infected in vitro with this recombinant adenovirus secreted significant amounts of functional IL-2 as tested on CTL-L2 cells. Furthermore, when injected into syngeneic DBA/2 mice, the tumorigenic phenotype is lost in up to 80% of the animals. The rejection of the infected cells was host dependent, because co-injection at the same site or concomitant injection at the opposite side of the animal with a tumorigenic dose of noninfected P815 cells did not lead to tumor development in 50–70% of the mice. Moreover, protected animals developed a long-lasting state of immunization against the P815 tumor cells and their splenocytes were able to transfer the immunity to syngeneic naïve recipients. Future human gene therapy of cancer will likely include different types of vectors well-adapted for in vivo gene transfer. Haddada et al. establish the feasibility of transferring a therapeutic gene to tumor cells with a replication-defective adenovirus vector. As a first step, they show that prior infection with a recombinant adenovirus expressing murine IL-2 of tumorigenic P815 mastocytes induces their rejection in 80% of injected DBA/2 mice. Moreover, animals are protected against subsequent tumor cell challenge and the protective immunity can be transferred by spleen cells to naïve mice. These results suggest that an adenovirus-based vector, despite the fact it is maintained mainly in an extrachromosomal form, could be used to transfer directly to tumors cytokine genes that could stimulate the immune response.