Immunotherapy of breast cancer by single delivery with rAAV2-mediated interleukin-15 expression.
Recombinant adenovirus-associated vector serotype 2 (rAAV2) is one of the most promising gene transfer vectors due to its advantage of causing non-pathogenic infection, low immunogenicity, and long-term gene expression in human clinical trials. Human interleukin 15 (hIL15) has been implicated in modulation of antitumor activity of lymphokine-activated killer (LAK) cells, including T cells and NK cells. In this study, the rAAV2-hIL15 vector was produced and subjected for treatment with xenograft JC breast cancer model. Results showed that tumor onset was significantly delayed, the tumor growth was suppressed, and the lifespan of tumor-bearing mice were prolonged by rAAV2-hIL15. In addition, rAAV2-hIL15 was able to produce a substantial expression of IL15 protein that ultimately activated the cytotoxic activity of LAK cells. Furthermore, prominent apoptosis was observed in tumor lesions following injection of rAAV2-hIL15. Taken together, our results suggested that rAAV2-hIL15 appears as a new potential therapeutic tool for breast cancer immunotherapy.
Yu
Yung-Luen
YL
Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University and Hospital, Taichung, Taiwan, ROC.
Wei
Chyou-Wei
CW
Chen
Yi-Lin
YL
Chen
Mark Hung-Chih
MH
Yiang
Giou-Teng
GT
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D020287:In Situ Nick-End Labeling; D019409:Interleukin-15 / Q000235:genetics / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
D019409:Interleukin-15