Personalized neoantigen-pulsed dendritic cell vaccines show superior immunogenicity to neoantigen-adjuvant vaccines in mouse tumor models

被引:58
|
作者
Zhang, Rui [1 ,2 ]
Yuan, Fengjiao [1 ,2 ]
Shu, Yang [3 ,4 ,5 ]
Tian, Yaomei [1 ,2 ]
Zhou, Bailing [1 ,2 ]
Yi, Linglu [1 ,2 ]
Zhang, Xueyan [1 ,2 ]
Ding, Zhenyu [6 ]
Xu, Heng [3 ,4 ,5 ]
Yang, Li [1 ,2 ]
机构
[1] West China Hosp, State Key Lab Biotherapy, 17,Sect 3,South Renmin Rd, Chengdu 610041, Sichuan, Peoples R China
[2] West China Hosp, Ctr Canc, Collaborat Innovat Ctr Biotherapy, 17,Sect 3,South Renmin Rd, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, State Key Lab Biotherapy, Precis Med Ctr, West China Hosp, Chengdu, Sichuan, Peoples R China
[4] Sichuan Univ, Precis Med Key Lab Sichuan Prov, Precis Med Ctr, West China Hosp, Chengdu, Sichuan, Peoples R China
[5] Collaborat Innovat Ctr, Chengdu, Sichuan, Peoples R China
[6] Sichuan Univ, State Key Lab Biotherapy, West China Med Sch, Ctr Canc,West China Hosp, Chengdu, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
Personalized neoantigens; Neoantigen-pulsed DC vaccines; Neoantigen-adjuvant vaccines; Immune response; Anti-tumor; CANCER-IMMUNOTHERAPY; INJECTION SITE; ANTIGEN; VACCINATION; MUTATIONS; TOLERANCE; MECHANISM; TIME;
D O I
10.1007/s00262-019-02448-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Development of personalized cancer vaccines based on neoantigens has become a new direction in cancer immunotherapy. Two forms of cancer vaccines have been widely studied: tumor-associated antigen (including proteins, peptides, or tumor lysates)-pulsed dendritic cell (DC) vaccines and protein- or peptide-adjuvant vaccines. However, different immune modalities may produce different therapeutic effects and immune responses when the same antigen is used. Therefore, it is necessary to choose a more effective neoantigen vaccination method. In this study, we compared the differences in immune and anti-tumor effects between neoantigen-pulsed DC vaccines and neoantigen-adjuvant vaccines using murine lung carcinoma (LL2) candidate neoantigens. The enzyme-linked immunospot (ELISPOT) assay showed that 4/6 of the neoantigen-adjuvant vaccines and 6/6 of the neoantigen-pulsed DC vaccines induced strong T-cell immune responses. Also, 2/6 of the neoantigen-adjuvant vaccines and 5/6 of the neoantigen-pulsed DC vaccines exhibited potent anti-tumor effects. The results indicated that the neoantigen-pulsed DC vaccines were superior to the neoantigen-adjuvant vaccines in both activating immune responses and inhibiting tumor growth. Our fundings provide an experimental basis for the selection of immune modalities for the use of neoantigens in individualized tumor immunotherapies.
引用
收藏
页码:135 / 145
页数:11
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