Optimization of whole-cell vaccines with CpG/αOX40/cGAMP to strengthen the anti-tumor response of CD4+ T cells in melanomas

被引:1
作者
Du, Xuedan [1 ]
Wu, Jinting [2 ]
Zhao, Ye [3 ]
Wang, Bin [2 ]
Ding, Xiaobo [2 ]
Lin, Qiuyan [4 ]
Chen, Yingyu [5 ]
Zhao, Jinduo [3 ]
Liu, Lixiao [3 ]
Mao, Xiaolu [2 ]
Fang, Zhen [2 ]
Zhang, Chunhong [6 ]
Li, Wenfeng [2 ]
机构
[1] Lishui Cent Hosp, Dept Oncol, Lishui, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Dept Oncol, Affiliated Hosp 1, 2 Fuxue Rd, Wenzhou 325000, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Dept Obstet & Gynecol, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China
[4] Ruian City Peoples Hosp, Dept Oncol, Wenzhou, Zhejiang, Peoples R China
[5] Wenzhou Med Univ, Dept Neurosurg, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China
[6] Wenzhou Med Univ, Dept Pharm, Affiliated Hosp 1, Wenzhou, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Whole-cell vaccines; CpG; OX40; agonist; cGAMP; Melanoma; CYTOKINE RELEASE; PD-1; BLOCKADE; TUMOR-GROWTH; CANCER; ACTIVATION; INJECTION; COMBINATION; DEATH; COSTIMULATION; ERADICATION;
D O I
10.1007/s00432-022-04117-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Methods In this study, we developed a strategy for the prevention and therapy of melanoma using a whole-cell vaccine combined with a CpG/alpha OX40/cGAMP triple adjuvant. The CpG/alpha OX40/cGAMP triple adjuvant was used to co-culture melanoma cells in vitro to induce immunogenic death of tumor cells. The mixture of inactivated tumor cells and the triple drug was an optimized tumor whole-cell vaccine, which was injected subcutaneously into mice for tumor prevention and therapy. Furthermore, we analyzed the changes of immune cells in spleen and tumor by flow cytometry and immunohistochemistry, and detected the changes of cytokines after vaccine application by cytometric bead array to explore the specific mechanism of vaccine. Results In vaccine prevention and therapy experiments, it was observed that the tumor growth was significantly inhibited in the whole-cell vaccine group, and the survival time of mice was significantly prolonged. Flow cytometry results showed that the proportion of CD4+ T cells and CD8+ T cells in tumor of mice in vaccine group was higher than that in control group, especially the CD4+ T cells. Conclusion The optimized vaccine has the unique ability to amplify tumor-specific CD4+ T cells, which improves antitumor sensitivity, and has a significant effect on the prevention and therapy of melanoma mice.
引用
收藏
页码:3337 / 3350
页数:14
相关论文
共 57 条
  • [1] The use of immunotherapy in the treatment of melanoma
    Achkar, Tala
    Tarhini, Ahmad A.
    [J]. JOURNAL OF HEMATOLOGY & ONCOLOGY, 2017, 10
  • [2] Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells
    Ahn, Jeonghyun
    Xia, Tianli
    Capote, Ailem Rabasa
    Betancourt, Dillon
    Barber, Glen N.
    [J]. CANCER CELL, 2018, 33 (05) : 862 - +
  • [3] Cytokine release syndrome after radiation therapy: case report and review of the literature
    Barker, Christopher A.
    Kim, Samuel K.
    Budhu, Sadna
    Matsoukas, Konstantina
    Daniyan, Anthony F.
    D'Angelo, Sandra P.
    [J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2018, 6
  • [4] Robust immune response stimulated by in situ injection of CpG/αOX40/cGAMP in αPD-1-resistant malignancy
    Cai, Luya
    Du, Xuedan
    Zhang, Cheng
    Yu, Shanshan
    Liu, Lixiao
    Zhao, Jinduo
    Zhao, Ye
    Zhang, Chunhong
    Wu, Jinting
    Wang, Bin
    Chen, Yingyu
    Su, Xiaoping
    Yan, Xiaojian
    Li, Wenfeng
    [J]. CANCER IMMUNOLOGY IMMUNOTHERAPY, 2022, 71 (07) : 1597 - 1609
  • [5] Chatenoud L, 1991, Curr Top Microbiol Immunol, V174, P121
  • [6] Parenteral immunization with a cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) adjuvanted Helicobacter pylori vaccine induces protective immunity against H. pylori infection in mice
    Chen, Jing
    Zhong, Youxiu
    Liu, Yu
    Tang, Chongfa
    Zhang, Yanbin
    Wei, Bo
    Chen, Wangxue
    Liu, Meiying
    [J]. HUMAN VACCINES & IMMUNOTHERAPEUTICS, 2020, 16 (11) : 2849 - 2854
  • [7] Whole tumor antigen vaccines
    Chiang, Cheryl Lai-Lai
    Benencia, Fabian
    Coukos, George
    [J]. SEMINARS IN IMMUNOLOGY, 2010, 22 (03) : 132 - 143
  • [8] Various ways to improve whole cancer cell vaccines
    Cicchelero, Laetitia
    de Rooster, Hilde
    Sanders, Niek N.
    [J]. EXPERT REVIEW OF VACCINES, 2014, 13 (06) : 721 - 735
  • [9] Immunization with mannosylated nanovaccines and inhibition of the immune-suppressing microenvironment sensitizes melanoma to immune checkpoint modulators
    Conniot, Joao
    Scomparin, Anna
    Peres, Carina
    Yeini, Eilam
    Pozzi, Sabina
    Matos, Ana, I
    Kleiner, Ron
    Moura, Liane I. F.
    Zupancic, Eva
    Viana, Ana S.
    Doron, Hila
    Gois, Pedro M. P.
    Erez, Neta
    Jung, Steffen
    Satchi-Fainaro, Ronit
    Florindo, Helena F.
    [J]. NATURE NANOTECHNOLOGY, 2019, 14 (09) : 891 - +
  • [10] Cytokine storm induced by a PD1 inhibitor in a renal transplant patient
    Del Bello, Arnaud
    Zakaroff, Alexia G.
    Meyer, Nicolas
    Delas, Audrey
    Faguer, Stanislas
    Kamar, Nassim
    Belliere, Julie
    [J]. AMERICAN JOURNAL OF TRANSPLANTATION, 2021, 21 (07) : 2616 - 2618