IL15 combined with Caspy2 provides enhanced therapeutic efficiency against murine malignant neoplasm growth and metastasis

• Published in: Cancer gene therapy Vol. 19; no. 7; pp. 460 - 467
• Main Authors: Yang, Y, Zhang, X-M, Zhang, N, Cheng, L, Li, C, Zhang, S, Zhang, J-F, Dai, L, Tian, H-W, Yan, N, Fan, P, Dai, L-X, Xu, F, Shi, G, Chen, X-L, Du, T, Li, Y-M, Wei, Y-Q, Deng, H-X
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2012
• Subjects: Analysis; Animal models; Animals; Antitumor activity; Apoptosis; Caspase; Caspases - genetics; Caspases - metabolism; Cell Line, Tumor; Cholesterol; Cytotoxicity; Cytotoxicity, Immunologic; DNA nucleotidylexotransferase; Down-Regulation; Female; Gene therapy; Genetic Therapy - methods; Immune response; Interleukin 1; Interleukin 10; Interleukin 15; Interleukin-15 - genetics; Interleukin-15 - metabolism; Interleukin-5; Labeling; Liposomes; Lung Neoplasms - genetics; Lung Neoplasms - secondary; Lung Neoplasms - therapy; Lymphocytes T; Metastases; Metastasis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasia; Neoplasm Transplantation; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Neoplasms, Experimental - therapy; Physiological aspects; T-Lymphocytes, Cytotoxic - metabolism; Tumor necrosis factor-α; Tumor suppression; Tumors; γ-Interferon
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/cgt.2012.17

Interleukin-15 (IL15) is a potential immunotherapeutic treatment for cancer. Caspy2 is an active zebra caspase for inducing apoptosis and immune response in murine tumors. In this study, we aim to evaluate the potential of gene therapy using IL15 and Caspy2 against the murine tumors. Plasmid expressing both Caspy2 and IL15 genes was constructed, encapsulated in DOTAP/cholesterol cationic liposome and injected intratumorally into the mice bearing CT26, B16-F10 and 4T1 carcinoma. We found that coexpression of IL15 and Caspy2 could significant inhibit tumor growth and prolong survival of the mice bearing CT26 or B16F10 tumor. A significant reduction in spontaneous lung metastasis was observed in the 4T1 tumor model. In CT26 model, the mice treated with IL15 and Caspy2 acquired a long-time protective immunity against the parental tumor cell rechallenge. Cytotoxic T lymphocytes and terminal deoxynucleotidyltransferase-mediated nick end labelling assays showed that the combination of capsy2 and IL15 could enhance both the apoptosis and immune response induction, which may account for its extraordinary antitumor effect. Furthermore, we showed that the observed tumor suppression by IL15 and Caspy2 concurred with the Caspy2-mediated downregulation of IL10 and upregulation of interferon-γ and tumor necrosis factor-α. Our results therefore suggested that the combination regimen might be a novel and effective strategy for cancer treatment.