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 50 条
  • [31] OX40 and CD30 signals in CD4+ T-cell effector and memory function: a distinct role for lymphoid tissue inducer cells in maintaining CD4+ T-cell memory but not effector function
    Withers, David R.
    Gaspal, Fabrina M.
    Bekiaris, Vasileios
    McConnell, Fiona M.
    Kim, MiYeon
    Anderson, Graham
    Lane, Peter J. L.
    IMMUNOLOGICAL REVIEWS, 2011, 244 : 134 - 148
  • [32] OX40 regulates pressure overload-induced cardiac hypertrophy and remodelling via CD4+ T-cells
    Wu, Qing-Qing
    Yuan, Yuan
    Jiang, Xiao-Han
    Xiao, Yang
    Yang, Zheng
    Ma, Zhen-Guo
    Liao, Hai-Han
    Liu, Yuan
    Chang, Wei
    Bian, Zhou-Yan
    Tang, Qi-Zhu
    CLINICAL SCIENCE, 2016, 130 (22) : 2061 - 2071
  • [33] OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells
    Yamaki, Satoshi
    Ine, Shouji
    Kawabe, Takeshi
    Okuyama, Yuko
    Suzuki, Nobu
    Soroosh, Pejman
    Mousavi, Seyed Fazlollah
    Nagashima, Hiroyuki
    Sun, Shu-lan
    So, Takanori
    Sasaki, Takeshi
    Harigae, Hideo
    Sugamura, Kazuo
    Kudo, Hironori
    Wada, Motoshi
    Nio, Masaki
    Ishii, Naoto
    EUROPEAN JOURNAL OF IMMUNOLOGY, 2014, 44 (10) : 3015 - 3025
  • [34] Enhanced T Cell-Independent Anti-tumor Effect of Cyclophosphamide Combined With Anti-CD40 MAB and CpG
    Johnson, Erik E.
    Buhtoiarov, Ilia N.
    Waisbren, Julie B.
    Sondel, Paul M.
    Rakhmilevich, Alexander L.
    JOURNAL OF IMMUNOTHERAPY, 2008, 31 (09) : 954 - 954
  • [35] Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis
    Fouladi, S.
    Masjedi, M.
    Hakemi, M. G.
    Ghasemi, R.
    Eskandari, N.
    ALLERGOLOGIA ET IMMUNOPATHOLOGIA, 2019, 47 (03) : 234 - 240
  • [36] Engagement of OX40 enhances antigen-specific CD4+ T cell mobilization/memory development and humoral immunity:: Comparison of αOX-40 with αCTLA-4
    Evans, DE
    Prell, RA
    Thalhofer, CJ
    Hurwitz, AA
    Weinberg, AD
    JOURNAL OF IMMUNOLOGY, 2001, 167 (12): : 6804 - 6811
  • [37] CD4 T cell traffic control:: in vivo evidence that ligation of OX40 on CD4 T cells by OX40-ligand expressed on dendritic cells leads to the accumulation of CD4 T cells in B follicles
    Brocker, T
    Gulbranson-Judge, A
    Flynn, S
    Riedinger, M
    Raykundalia, C
    Lane, P
    EUROPEAN JOURNAL OF IMMUNOLOGY, 1999, 29 (05) : 1610 - 1616
  • [38] Increased frequency and activation of CD4+ T cells enhances anti-tumor immunity.
    Brown, DM
    Woodward, JG
    Frelinger, JG
    Lord, EM
    FASEB JOURNAL, 2000, 14 (06): : A1015 - A1015
  • [39] Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer
    Oh, David Y.
    Kwek, Serena S.
    Raju, Siddharth S.
    Li, Tony
    McCarthy, Elizabeth
    Chow, Eric
    Aran, Dvir
    Ilano, Arielle
    Pai, Chien-Chun Steven
    Rancan, Chiara
    Allaire, Kathryn
    Burra, Arun
    Sun, Yang
    Spitzer, Matthew H.
    Mangul, Serghei
    Porten, Sima
    Meng, Maxwell, V
    Friedlander, Terence W.
    Ye, Chun Jimmie
    Fong, Lawrence
    CELL, 2020, 181 (07) : 1612 - +
  • [40] OX40 contributes to the CD4+T cell proliferation induced by human allogeneic endothelial cells.
    Camara, NOS
    Cappellesso, S
    Watier, H
    Lebranchu, Y
    TRANSPLANTATION, 1999, 67 (07) : S133 - S133