PMID- 35795680 OWN - NLM STAT- MEDLINE DCOM- 20220708 LR - 20220720 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - A Novel PD-L1-Containing MSLN Targeting Vaccine for Lung Cancer Immunotherapy. PG - 925217 LID - 10.3389/fimmu.2022.925217 [doi] LID - 925217 AB - Therapeutic tumor vaccines have become an important breakthrough in the treatment of various solid tumors including lung cancer. Dendritic cells (DCs)-based tumor vaccines targeting tumor-associated antigens (TAAs) play a key role in immunotherapy and immunoprevention. However, the weak immunogenicity of TAAs and low immune response rates are a major challenge faced in the application of therapeutic tumor vaccines. Here, we tested whether targeting an attractive target Mesothelin (MSLN) and PD-L1 immune checkpoint molecule to DCs in vivo would elicit therapeutic antitumor cytotoxic T lymphocyte (CTL) response. We generated specific MSLN fragment combined with PD-L1 and GM-CSF peptide immunogen (MSLN-PDL1-GMCSF) based on the novel anti-PD-L1 vaccination strategy we recently developed for the cancer treatment and prevention. We found that DCs loaded with MSLN-PDL1-GMCSF vaccine elicited much stronger endogenous anti-PD-L1 antibody and T cell responses in immunized mice and that antigen specific CTLs had cytolytic activities against tumor cells expressing both MSLN and PD-L1. We demonstrated that vaccination with MSLN-PDL1-GMCSF potently inhibited the tumor growth of MSLN(+) and PD-L1(+) lung cancer cells, exhibiting a significant therapeutic anti-tumor potential. Furthermore, PD-1 blockade further improved the synergistic antitumor therapeutic efficacy of MSLN-PDL1-GMCSF vaccine in immunized mice. In summary, our data demonstrated for the first time that this PD-L1-containing MSLN therapeutic vaccine can induce persistent anti-PD-L1 antibody and CTL responses, providing an effective immunotherapeutic strategy for lung cancer immunotherapy by combining MSLN-PDL1-GMCSF vaccine and PD-1 blockade. CI - Copyright (c) 2022 Zeng, Pan, Fang, Jia, Zhang, He, Zhong, He, Yang, Shi, Zhong, Zeng, Fu, Huang and Liu. FAU - Zeng, Wuyi AU - Zeng W AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Pan, Jiayi AU - Pan J AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Fang, Zixuan AU - Fang Z AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Jia, Jiangtao AU - Jia J AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Zhang, Rong AU - Zhang R AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - He, Menghua AU - He M AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Zhong, Hanyu AU - Zhong H AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - He, Jiashan AU - He J AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Yang, Xinyu AU - Yang X AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Shi, Yi AU - Shi Y AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Zhong, Bei AU - Zhong B AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Zeng, Jun AU - Zeng J AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Fu, Bishi AU - Fu B AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. AD - The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Guangzhou, China. FAU - Huang, Maoping AU - Huang M AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. FAU - Liu, Hui AU - Liu H AD - School of Basic Medical Sciences, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, China. AD - The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Guangzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220620 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (Immunologic Factors) RN - 0 (Programmed Cell Death 1 Receptor) RN - J27WDC343N (Mesothelin) SB - IM MH - Animals MH - Antigens, Neoplasm MH - *Cancer Vaccines MH - Immunologic Factors MH - Immunotherapy MH - *Lung Neoplasms/therapy MH - Mesothelin MH - Mice MH - Programmed Cell Death 1 Receptor PMC - PMC9251065 OTO - NOTNLM OT - MSLN OT - PD-L1 OT - dendritic cells OT - immunotherapy OT - therapeutic vaccine COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/08 06:00 MHDA- 2022/07/09 06:00 PMCR- 2022/01/01 CRDT- 2022/07/07 02:34 PHST- 2022/04/21 00:00 [received] PHST- 2022/05/23 00:00 [accepted] PHST- 2022/07/07 02:34 [entrez] PHST- 2022/07/08 06:00 [pubmed] PHST- 2022/07/09 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.925217 [doi] PST - epublish SO - Front Immunol. 2022 Jun 20;13:925217. doi: 10.3389/fimmu.2022.925217. eCollection 2022.