Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3K gamma inhibitor can enhance immunogenicity and eradicate tumors

doi:10.1136/jitc-2021-003564

	Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3K gamma inhibitor can enhance immunogenicity and eradicate tumors
	Du, Yang1,2 ; Liu, Ye 3; Wang, Di 4; Bai, Hua 4; Wang, Zhijie 4; He, Xiran 1,4; Zhang, Pei 1,4; Tian, Jie 1,2,5,6; Wang, Jie 4
发表期刊	JOURNAL FOR IMMUNOTHERAPY OF CANCER
	2022-02-01
卷号	10 期号:2 页码:13
通讯作者	Tian, Jie(jie.tian@ia.ac.cn) ; Wang, Jie(zlhuxi@163.com)
摘要	Background With the rapid development of immune checkpoint inhibitors and neoantigen (NeoV)-based personalized tumor vaccines, tumor immunotherapy has shown promising therapeutic results. However, the limited efficacy of available tumor vaccines impedes the development of personalized tumor immunotherapy. In this study, we developed a novel tumor vaccine system and proposed combined therapeutic strategies for improving treatment effects. Methods We developed a novel tumor vaccine system comprising a newly synthesized peptidic microarchitecture (PMA) with high assembly efficacy. The PMA-trapped neoantigen vaccine was developed to codeliver tumor neoantigen and the Toll-like receptor 9 agonist CpG (NeoV), abbreviated as PMA-NeoV. A microfluidic chip was used to produce PMA particles in a uniform and precise manner. Vaccine effectiveness was investigated both in vitro and in vivo. The combined immunotherapeutic effect of PMA-NeoV with anti-programmed cell death ligand 1 antibody (aPD-L1) or with the phosphatidylinositol 3-kinase gamma (PI3K gamma) inhibitor IPI-549 was further tested in MC38 mouse tumor model. Results PMA-NeoV not only promoted codelivery of the tumor vaccine but also potentiated vaccine immunogenicity. Moreover, compared with free NeoV, PMA-NeoV significantly increased the number of tumor-infiltrating lymphocytes, promoted the neoantigen-specific systemic immune response, and suppressed murine colon MC38 tumor growth. Furthermore, PMA-NeoV increased the expression of programmed cell death receptor-1 on T lymphocytes, and in combination with aPD-L1 eradicated seven of eight MC38 tumors by rescuing exhausted T lymphocytes. Moreover, we combined the PMA-NeoV with the IPI-549, a molecular switch that controls immune suppression, and found that this combination significantly suppressed tumor growth and eradicated five of eight inoculated tumors, by switching suppressive macrophages to their active state and activating T cells to prime a robust tumor immune microenvironment. Conclusions We developed a tumor vaccine delivery system and presented a promising personalized tumor vaccine-based therapeutic regimen in which a tumor vaccine delivery system is combined with an aPD-L1 or PI3K gamma inhibitor to improve tumor immunotherapy outcomes.
关键词	immunotherapy immunogenicity vaccine tumor microenvironment lymphocytes tumor infiltrating macrophages
DOI	10.1136/jitc-2021-003564
关键词[WOS]	CANCER ; BLOCKADE ; RESPONSES ; MUTANOME ; EFFICACY ; CELLS
收录类别	SCI
语种	英语
资助项目	Beijing Natural Science Foundation[7212207] ; National Natural Science Foundation of China[81871514] ; National Natural Science Foundation of China[92159303] ; National Natural Science Foundation of China[62027901] ; National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[81470083] ; National Natural Science Foundation of China[81527805] ; Ministry of Science and Technology of China[2017YFA0205200] ; Ministry of Science and Technology of China[2017YFA0700401] ; National Key Research and Development Program of China[2017YFA0700401] ; Leading Medical Talents Program of Health Commission of Yunnan Province[L-2018013] ; Young and Middle Aged Academic and Technical Leaders Program of Yunnan Province[202005AC160010]
项目资助者	Beijing Natural Science Foundation ; National Natural Science Foundation of China ; Ministry of Science and Technology of China ; National Key Research and Development Program of China ; Leading Medical Talents Program of Health Commission of Yunnan Province ; Young and Middle Aged Academic and Technical Leaders Program of Yunnan Province
WOS研究方向	Oncology ; Immunology
WOS类目	Oncology ; Immunology
WOS记录号	WOS:000762406500006
出版者	BMJ PUBLISHING GROUP
七大方向——子方向分类	其他
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.ia.ac.cn/handle/173211/48033
专题	中国科学院分子影像重点实验室
通讯作者	Tian, Jie; Wang, Jie
作者单位	1.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing Key Lab Mol Imaging,State Key Lab Managem, Beijing, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Med Sci, Peking Union Med Coll, Inst Med Biol, Kunming, Yunnan, Peoples R China 4.Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Dept Med Oncol, Natl Clin Res Ctr Canc,Canc Hosp, Beijing, Peoples R China 5.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Med, Beijing, Peoples R China 6.Xidian Univ, Sch Life Sci & Technol, Xian, Shaanxi, Peoples R China
第一作者单位	中国科学院自动化研究所
通讯作者单位	中国科学院自动化研究所
推荐引用方式 GB/T 7714	Du, Yang,Liu, Ye,Wang, Di,et al. Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3K gamma inhibitor can enhance immunogenicity and eradicate tumors[J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER,2022,10(2):13.
APA	Du, Yang.,Liu, Ye.,Wang, Di.,Bai, Hua.,Wang, Zhijie.,...&Wang, Jie.(2022).Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3K gamma inhibitor can enhance immunogenicity and eradicate tumors.JOURNAL FOR IMMUNOTHERAPY OF CANCER,10(2),13.
MLA	Du, Yang,et al."Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3K gamma inhibitor can enhance immunogenicity and eradicate tumors".JOURNAL FOR IMMUNOTHERAPY OF CANCER 10.2(2022):13.