title: Forced co-expression of IL-21 and IL-7 in whole-cell cancer vaccines promotes antitumor immunity.
abstract: 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.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Yang-Zhuo
authors: YZ
authors: Gu
authors: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.|Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.|Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Chuan-Wen
authors: CW
authors: Fan
authors: Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Ran
authors: R
authors: Lu
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Bin
authors: B
authors: Shao
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Ya-Xiong
authors: YX
authors: Sang
authors: Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Qiao-Rong
authors: QR
authors: Huang
authors: Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Xue
authors: X
authors: Li
authors: Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Wen-Tong
authors: WT
authors: Meng
authors: Laboratory of Stem Cell Biology and Department of Pediatric Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Xian-Ming
authors: XM
authors: Mo
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors: Yu-Quan
authors: YQ
authors: Wei
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D000098546:Interleukin-21
chemical_list: D019496:Cancer Vaccines; D015851:Interleukin-7; D007378:Interleukins; D000098546:Interleukin-21