Forced co-expression of IL-21 and IL-7 in whole-cell cancer vaccines promotes antitumor immunity

• Published in: Scientific reports Vol. 6; no. 1; p. 32351
• Main Authors: Gu, Yang-Zhuo, Fan, Chuan-Wen, Lu, Ran, Shao, Bin, Sang, Ya-Xiong, Huang, Qiao-Rong, Li, Xue, Meng, Wen-Tong, Mo, Xian-Ming, Wei, Yu-Quan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.08.2016; Nature Publishing Group
• Subjects: 13/106; 13/109; 13/44; 631/67/1059/2325; 692/4028/67/1059/2325; Animal models; Animals; Cancer; Cancer vaccines; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytokines; Effector cells; Gene Expression Regulation, Neoplastic - immunology; Humanities and Social Sciences; Humans; Immune response; Immunity, Cellular - genetics; Immunological memory; Immunotherapy; Infiltration; Interleukin 21; Interleukin 7; Interleukin-7 - genetics; Interleukin-7 - immunology; Interleukins - genetics; Interleukins - immunology; Long-term effects; Lymphocytes; Lymphocytes T; Memory cells; Mice; Mice, Knockout; multidisciplinary; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - prevention & control; Neoplasms, Experimental - genetics; Neoplasms, Experimental - immunology; Neoplasms, Experimental - prevention & control; Science; Science (multidisciplinary); Vaccines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep32351

Genetic modification of whole-cell cancer vaccines to augment their efficacies has a history of over two and a half decades. Various genes and gene combinations, targeting different aspects of immune responses have been tested in pursuit of potent adjuvant effects. Here we show that co-expression of two cytokine members of the common cytokine receptor γ-chain family, IL-21 and IL-7, in whole-cell cancer vaccines boosts antitumor immunity in a CD4 + and CD8 + T cell-dependent fashion. It also generates effective immune memory. The vaccine-elicited short-term effects positively correlated with enhanced infiltration of CD4 + and CD8 + effector T cells, and the long-term effects positively correlated with enhanced infiltration of effector memory T cells, especially CD8 + effector memory T cells. Preliminary data suggested that the vaccine exhibited good safety profile in murine models. Taken together, the combination of IL-21 and IL-7 possesses potent adjuvant efficacy in whole-cell vaccines. This finding warrants future development of IL-21 and IL-7 co-expressing whole-cell cancer vaccines and their relevant combinatorial regimens.