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

Abstract

Abstract. Human interleukin-15 (hIL15) exerts anticancer effects through the activities of lymphokine-activated killer (LAK) cells. However, its short half-life hinders its clinical application. Recombinant adeno-associated virus serotype 2 (rAAV2) is used for hIL15 gene transfer vectors, because of its low immunogenicity and long-term gene expression in human clinical trials. SV40 T/t antigens are related with 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-induced breast cancer, rAAV2-hIL15 was constructed and an SV40 T/t antigen-induced transgenic mouse breast cancer model was established. Our study showed that rAAV2-hIL15 could express the hIL15 protein with anticancer bioactivity. In addition, rAAV2-hIL15 could activate the cytotoxic activity of LAK cells in vivo. Furthermore, the rAAV2-hIL15 successfully delayed cancer growth and eventually led to cancer cell death in SV40 T/t antigen-induced breast cancer transgenic mice. In summary, our study indicates that rAAV2-hIL15 may be applied for cancer immunotherapy of SV40 T/t antigen-induced breast cancer.

Adeno-associated virus (AAV) vectors in cancer gene therapy

“…Analogously, therapeutic delivery (vector delivered to tumor-bearing mice) led to both 80% lower tumor metastasis and enhanced mean survival by 41% with no apparent liver toxicity observed. Another group intramuscularly administered AAV2-IL15 to a transgenic model of SV40 T/t antigen-induced breast cancer prior to induction of breast cancer, which stimulated lymphokine-activated killer (LAK) cells, slowed tumor growth (tumor size reached 2500 mm 3 after 33 days vs. 20 days for control) and reduced final tumor size by 30% [132]. …”