Immunotherapy for SV40 T/t antigen-induced breast cancer by recombinant adeno-associated virus serotype 2 carrying interleukin-15 in mice

Human interleukin-15 (hIL15) exerts anticancer effects through the activitiesof lymphokine-activated killer (LAK) cells. However, its short half-life hindersits clinical application. Recombinant adeno-associated virus serotype 2 (rAAV2)is used for hIL15 gene transfer vectors, because of its low immunogenicity andlong-term gene expression in human clinical trials. SV40 T/t antigens are relatedwith many human epithelial cancers and are generally found in human breast cancer.In order to demonstrate the anticancer effects of hIL15 on SV40 T/t antigen-inducedbreast cancer, rAAV2-hIL15 was constructed and an SV40 T/t antigen-induced transgenicmouse breast cancer model was established. Our study showed that rAAV2-hIL15 couldexpress the hIL15 protein with anticancer bioactivity. In addition, rAAV2-hIL15could activate the cytotoxic activity of LAK cells in vivo. Furthermore, the rAAV2-hIL15successfully delayed cancer growth and eventually led to cancer cell death inSV40 T/t antigen-induced breast cancer transgenic mice. In summary, our studyindicates that rAAV2-hIL15 may be applied for cancer immunotherapy of SV40 T/tantigen-induced breast cancer.