PMID- 35547749 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220716 IS - 1838-7640 (Electronic) IS - 1838-7640 (Linking) VI - 12 IP - 7 DP - 2022 TI - Optimized mobilization of MHC class I- and II- restricted immunity by dendritic cell vaccine potentiates cancer therapy. PG - 3488-3502 LID - 10.7150/thno.71760 [doi] AB - Background: The participation of major histocompatibility complex (MHC) in antigen presentation shapes both the breadth and magnitude of specific T cell response. Dendritic cells (DCs) activated with nucleic acid or protein that encodes/incorporates multiple antigenic epitopes elicit MHC class I- and II- biased immunity, respectively. Studies demonstrate that an elevated MHC class I-directed CD8(+) cytotoxicity T lymphocyte (CTL) response is able to provide survival benefits to patient with malignant tumor. However, a fully effective cancer therapy must elicit a diverse repertoire of both CD4(+) and CD8(+) T cell responses, raising demands on a multifaceted activation of the MHC system. Current therapeutic strategies usually lack an orchestrated mobilization of the MHC class I and II responses. Vaccines with little synergistic effect or unmanageable elicitation of the CD4(+) and CD8(+) T cell immunity usually fail to induce a potent and durable anti-tumor protection. Methods: Here, cationic nanoemulsions (CNEs) complexed with full-length tumor model antigen ovalbumin (OVA) in the form of mRNA or protein were constructed and used as two antigenic platforms to prepare DCs vaccines with tailored MHC participation (i.e., mRNA-DCs and protein-DCs). In exploring a vaccine regimen with optimal tumor suppressing effect, the mixing ratio of mRNA-DCs and protein-DCs was manipulated. Results: Therapeutic DCs vaccines involving both antigenic platforms induced better anti-tumor immunity in murine E.G7-OVA lymphoma model and B16-OVA melanoma model, which can be further augmented upon a meticulous reallocation of the MHC class I and II responses. Conclusion: This work indicated that a simultaneous and coordinated mobilization of the MHC-restricted immunity might potentiate cancer therapy. CI - (c) The author(s). FAU - Shi, Yingying AU - Shi Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Liu, Yu AU - Liu Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Huang, Jiaxin AU - Huang J AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Luo, Zhenyu AU - Luo Z AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Guo, Xuemeng AU - Guo X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Jiang, Mengshi AU - Jiang M AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Li, Xiang AU - Li X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Lu, Yichao AU - Lu Y AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Liu, Xu AU - Liu X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Shan, Xinyu AU - Shan X AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - Luo, Lihua AU - Luo L AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. FAU - You, Jian AU - You J AD - College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220424 PL - Australia TA - Theranostics JT - Theranostics JID - 101552395 RN - 0 (Antigens, Neoplasm) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (RNA, Messenger) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - Antigens, Neoplasm MH - *CD4-Positive T-Lymphocytes MH - Dendritic Cells MH - Histocompatibility Antigens Class I MH - Humans MH - *Melanoma, Experimental MH - Mice MH - Mice, Inbred C57BL MH - Ovalbumin MH - RNA, Messenger/metabolism PMC - PMC9065178 OTO - NOTNLM OT - MHC-restricted immunity OT - cancer therapy OT - cationic nanoemulsions OT - mRNA-DCs OT - protein-DCs COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2022/05/14 06:00 MHDA- 2022/05/18 06:00 PMCR- 2022/01/01 CRDT- 2022/05/13 11:17 PHST- 2022/02/06 00:00 [received] PHST- 2022/03/12 00:00 [accepted] PHST- 2022/05/13 11:17 [entrez] PHST- 2022/05/14 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - thnov12p3488 [pii] AID - 10.7150/thno.71760 [doi] PST - epublish SO - Theranostics. 2022 Apr 24;12(7):3488-3502. doi: 10.7150/thno.71760. eCollection 2022.