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Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3K gamma inhibitor can enhance immunogenicity and eradicate tumors
Du, Yang1,2; Liu, Ye3; Wang, Di4; Bai, Hua4; Wang, Zhijie4; He, Xiran1,4; Zhang, Pei1,4; Tian, Jie1,2,5,6; Wang, Jie4
Source PublicationJOURNAL FOR IMMUNOTHERAPY OF CANCER
2022-02-01
Volume10Issue:2Pages:13
Corresponding AuthorTian, Jie(jie.tian@ia.ac.cn) ; Wang, Jie(zlhuxi@163.com)
AbstractBackground 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.
Keywordimmunotherapy immunogenicity vaccine tumor microenvironment lymphocytes tumor infiltrating macrophages
DOI10.1136/jitc-2021-003564
WOS KeywordCANCER ; BLOCKADE ; RESPONSES ; MUTANOME ; EFFICACY ; CELLS
Indexed BySCI
Language英语
Funding ProjectBeijing 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]
Funding OrganizationBeijing 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 Research AreaOncology ; Immunology
WOS SubjectOncology ; Immunology
WOS IDWOS:000762406500006
PublisherBMJ PUBLISHING GROUP
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/48033
Collection中国科学院分子影像重点实验室
Corresponding AuthorTian, Jie; Wang, Jie
Affiliation1.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
First Author AffilicationInstitute of Automation, Chinese Academy of Sciences
Corresponding Author AffilicationInstitute of Automation, Chinese Academy of Sciences
Recommended Citation
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.
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