PMID- 37079211 OWN - NLM STAT- MEDLINE DCOM- 20230829 LR - 20230829 IS - 1699-3055 (Electronic) IS - 1699-048X (Linking) VI - 25 IP - 10 DP - 2023 Oct TI - DC vaccine enhances CAR-T cell antitumor activity by overcoming T cell exhaustion and promoting T cell infiltration in solid tumors. PG - 2972-2982 LID - 10.1007/s12094-023-03161-1 [doi] AB - OBJECTIVE: Great success has been achieved in CAR-T cell immunotherapy in the treatment of hematological tumors. However, it is particularly difficult in solid tumors, because CAR-T is difficult to enter interior and exert long-term stable immune effects. Dendritic cells (DCs) can not only present tumor antigens but also promote the infiltration of T cells. Therefore, CAR-T cells with the help of DC vaccines are a reliable approach to treat solid tumors. METHODS: To test whether DC vaccine could promote CAR-T cell therapy in solid tumors, DC vaccine was co-cultured with MSLN CAR-T cells. The in vitro effects of DC vaccine on CAR-T were assessed by measuring cell proliferation, cell differentiation, and cytokine secretion. Effects of DC vaccine on CAR-T were evaluated using mice with subcutaneous tumors in vivo. The infiltration of CAR-T was analyzed using immunofluorescence. The persistence of CAR-T in mouse blood was analyzed using real-time quantitative PCR. RESULTS: The results showed that DC vaccine significantly enhanced the proliferation potential of MSLN CAR-T cells in vitro. DC vaccines not only promoted the infiltration of CAR-T cells, but also significantly improved the persistence of CAR-T in solid tumors in vivo. CONCLUSION: In conclusion, this study has demonstrated that DC vaccine can promote CAR-T therapy in solid tumors, which provides the possibility of widespread clinical application of CAR-T cells in the future. CI - (c) 2023. The Author(s), under exclusive licence to Federacion de Sociedades Espanolas de Oncologia (FESEO). FAU - Zhang, Miaomiao AU - Zhang M AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Wang, Yuanyuan AU - Wang Y AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Chen, Xinzu AU - Chen X AUID- ORCID: 0000-0001-5733-6179 AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Zhang, Fan AU - Zhang F AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Chen, Jiannan AU - Chen J AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Zhu, Hongqiao AU - Zhu H AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Li, Jun AU - Li J AD - Nanjing Blue Shield Biotechnology Co., Ltd., Nanjing, 210023, China. FAU - Chen, Zhengliang AU - Chen Z AD - Nanjing Blue Shield Biotechnology Co., Ltd., Nanjing, 210023, China. FAU - Wang, Aying AU - Wang A AD - Department of Respiratory and Critical Care Medicine, The First School of Clinical Medicine, Jinling Hospital, Southern Medical University, Nanjing, 210018, China. FAU - Xiao, Yao AU - Xiao Y AD - Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. FAU - Chen, Zilu AU - Chen Z AD - Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China. FAU - Dong, Yunfei AU - Dong Y AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Yin, Xuechen AU - Yin X AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Ji, Feng AU - Ji F AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Liu, Jie AU - Liu J AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Liang, Junqing AU - Liang J AD - Inner Mongolia Autonomous Region Cancer Hospital, Hohhot, 010010, China. FAU - Pan, Feiyan AU - Pan F AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - Guo, Zhigang AU - Guo Z AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. FAU - He, Lingfeng AU - He L AD - Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China. lfhe22@139.com. LA - eng GR - 81872284/National Natural Science Foundation of China/ PT - Journal Article DEP - 20230420 PL - Italy TA - Clin Transl Oncol JT - Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico JID - 101247119 RN - 0 (Receptors, Chimeric Antigen) RN - 0 (Vaccines) SB - IM MH - Mice MH - Animals MH - T-Lymphocytes MH - *Receptors, Chimeric Antigen MH - T-Cell Exhaustion MH - *Neoplasms/therapy MH - Immunotherapy, Adoptive/methods MH - *Vaccines OTO - NOTNLM OT - DC vaccine OT - Infiltration OT - MSLN CAR-T OT - Persistence OT - Solid tumor EDAT- 2023/04/20 13:41 MHDA- 2023/08/29 12:42 CRDT- 2023/04/20 11:21 PHST- 2023/02/27 00:00 [received] PHST- 2023/03/19 00:00 [accepted] PHST- 2023/08/29 12:42 [medline] PHST- 2023/04/20 13:41 [pubmed] PHST- 2023/04/20 11:21 [entrez] AID - 10.1007/s12094-023-03161-1 [pii] AID - 10.1007/s12094-023-03161-1 [doi] PST - ppublish SO - Clin Transl Oncol. 2023 Oct;25(10):2972-2982. doi: 10.1007/s12094-023-03161-1. Epub 2023 Apr 20.