Combination treatment of radiofrequency ablation and peptide neoantigen vaccination: Promising modality for future cancer immunotherapy

被引:17
作者
Shou, Jiawei [1 ]
Mo, Fan [2 ,3 ,4 ,5 ]
Zhang, Shanshan [2 ,6 ]
Lu, Lantian [2 ,7 ]
Han, Ning [2 ,8 ]
Liu, Liang [2 ]
Qiu, Min [2 ]
Li, Hongseng [1 ]
Han, Weidong [1 ]
Ma, Dongying [2 ]
Guo, Xiaojie [2 ]
Guo, Qianpeng [2 ]
Huang, Qinxue [2 ]
Zhang, Xiaomeng [2 ]
Ye, Shengli [9 ]
Pan, Hongming [1 ]
Chen, Shuqing [2 ,3 ,6 ,10 ]
Fang, Yong [1 ]
机构
[1] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Peoples R China
[2] Hangzhou Neoantigen Therapeut Co Ltd, Hangzhou, Peoples R China
[3] Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou, Peoples R China
[4] Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC, Canada
[5] Hangzhou AI Force Therapeut Co Ltd, Hangzhou, Peoples R China
[6] Zhejiang Univ, Zhejiang Calif Int Nanosyst Inst, Hangzhou, Peoples R China
[7] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia
[8] Hangzhou AI Nano Therapeut Co Ltd, Hangzhou, Peoples R China
[9] Shulan Hangzhou Hosp, Hangzhou, Peoples R China
[10] ZJU Hangzhou Global Sci & Technol Innovat Ctr, Hangzhou, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
中国国家自然科学基金;
关键词
neoantigen vaccine; radiofrequency ablation; immune checkpoint inhibition; cancer; immunotherapy; PHASE-III; INTERLEUKIN-6; RESPONSES;
D O I
10.3389/fimmu.2022.1000681
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundThe safety and immunogenicity of a personalized neoantigen-based peptide vaccine, iNeo-Vac-P01, was reported previously in patients with a variety of cancer types. The current study investigated the synergistic effects of radiofrequency ablation (RFA) and neoantigen vaccination in cancer patients and tumor-bearing mice. MethodsTwenty-eight cancer patients were enrolled in this study, including 10 patients who had received RFA treatment within 6 months before vaccination (Cohort 1), and 18 patients who had not (Cohort 2). Individualized neoantigen peptide vaccines were designed, manufactured, and subcutaneously administrated with GM-CSF as an adjuvant for all patients. Mouse models were employed to validate the synergistic efficacy of combination treatment of RFA and neoantigen vaccination. ResultsLonger median progression free survival (mPFS) and median overall survival (mOS) were observed in patients in Cohort 1 compared to patients in Cohort 2 (4.42 and 20.18 months vs. 2.82 and 10.94 months). The results of ex vivo IFN-gamma ELISpot assay showed that patients in Cohort 1 had stronger neoantigen-specific immune responses at baseline and post vaccination. Mice receiving combination treatment of RFA and neoantigen vaccines displayed higher antitumor immune responses than mice receiving single modality. The combination of PD-1 blockage with RFA and neoantigen vaccines further enhanced the antitumor response in mice. ConclusionNeoantigen vaccination after local RFA treatment could improve the clinical and immune response among patients of different cancer types. The synergistic antitumor potentials of these two modalities were also validated in mice, and might be further enhanced by immune checkpoint inhibition. The mechanisms of their synergies require further investigation.
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页数:16
相关论文
共 41 条
  • [1] Hepatic Radiofrequency Ablation-induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition
    Ahmed, Muneeb
    Kumar, Gaurav
    Moussa, Marwan
    Wang, Yuanguo
    Rozenblum, Nir
    Galun, Eithan
    Goldberg, S. Nahum
    [J]. RADIOLOGY, 2016, 279 (01) : 103 - 117
  • [2] Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells
    Baharom, Faezzah
    Ramirez-Valdez, Ramiro A.
    Tobin, Kennedy K. S.
    Yamane, Hidehiro
    Dutertre, Charles-Antoine
    Khalilnezhad, Ahad
    Reynoso, Glennys, V
    Coble, Vincent L.
    Lynn, Geoffrey M.
    Mule, Matthew P.
    Martins, Andrew J.
    Finnigan, John P.
    Zhang, Xiao Meng
    Hamerman, Jessica A.
    Bhardwaj, Nina
    Tsang, John S.
    Hickman, Heather D.
    Ginhoux, Florent
    Ishizuka, Andrew S.
    Seder, Robert A.
    [J]. NATURE IMMUNOLOGY, 2021, 22 (01) : 41 - 52
  • [3] Additive antitumour response to the rabbit VX2 hepatoma by combined radio frequency ablation and toll like receptor 9 stimulation
    Behm, Barbara
    Di Fazio, Pietro
    Michl, Patrick
    Neureiter, Daniel
    Kemmerling, Ralf
    Hahn, Eckhart Georg
    Strobel, Deike
    Gress, Thomas
    Schuppan, Detlef
    Wissniowski, Thaddaeus Till
    [J]. GUT, 2016, 65 (01) : 134 - 143
  • [4] Cytokine expression profile in human pancreatic carcinoma cells and in surgical specimens: implications for survival
    Bellone, G
    Smirne, C
    Mauri, FA
    Tonel, E
    Carbone, A
    Buffolino, A
    Dughera, L
    Robecchi, A
    Pirisi, M
    Emanuelli, G
    [J]. CANCER IMMUNOLOGY IMMUNOTHERAPY, 2006, 55 (06) : 684 - 698
  • [5] CTLA-4-mediated inhibition in regulation of T cell responses: Mechanisms and manipulation in tumor immunotherapy
    Chambers, CA
    Kuhns, MS
    Egen, JG
    Allison, JP
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2001, 19 : 565 - 594
  • [6] Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma
    Duffy, Austin G.
    Ulahannan, Susanna V.
    Makorova-Rusher, Oxana
    Rahma, Osama
    Wedemeyer, Heiner
    Pratt, Drew
    Davis, Jeremy L.
    Hughes, Marybeth S.
    Heller, Theo
    ElGindi, Mei
    Uppala, Ashish
    Korangy, Firouzeh
    Kleiner, David E.
    Figg, William D.
    Venzon, David
    Steinberg, Seth M.
    Venkatesan, Aradhana M.
    Krishnasamy, Venkatesh
    Abi-Jaoudeh, Nadine
    Levy, Elliot
    Wood, Brad J.
    Greten, Tim F.
    [J]. JOURNAL OF HEPATOLOGY, 2017, 66 (03) : 545 - 551
  • [7] A Pan-cancer Clinical Study of Personalized Neoantigen Vaccine Monotherapy in Treating Patients with Various Types of Advanced Solid Tumors
    Fang, Yong
    Mo, Fan
    Shou, Jiawei
    Wang, Huimin
    Luo, Kai
    Zhang, Shanshan
    Han, Ning
    Li, Hongsen
    Ye, Shengli
    Zhou, Zhan
    Chen, Rongchang
    Chen, Lin
    Liu, Liang
    Wang, Huina
    Pan, Hongming
    Chen, Shuqing
    [J]. CLINICAL CANCER RESEARCH, 2020, 26 (17) : 4511 - 4520
  • [8] High-dimensional single-cell analysis delineates radiofrequency ablation induced immune microenvironmental remodeling in pancreatic cancer
    Fei, Qinglin
    Pan, Yu
    Lin, Wenji
    Zhou, Yuanyuan
    Yu, Xingxing
    Hou, Zelin
    Yu, Xunbin
    Lin, Xianchao
    Lin, Ronggui
    Lu, Fengchun
    Guan, Hongdan
    Huang, Heguang
    [J]. CELL DEATH & DISEASE, 2020, 11 (07)
  • [9] Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients
    Gros, Alena
    Parkhurst, Maria R.
    Tran, Eric
    Pasetto, Anna
    Robbins, Paul F.
    Ilyas, Sadia
    Prickett, Todd D.
    Gartner, Jared J.
    Crystal, Jessica S.
    Roberts, Ilana M.
    Trebska-McGowan, Kasia
    Wunderlich, John R.
    Yang, James C.
    Rosenberg, Steven A.
    [J]. NATURE MEDICINE, 2016, 22 (04) : 433 - +
  • [10] Gros A, 2014, J CLIN INVEST, V124, P2246, DOI [10.1172/JC173639, 10.1172/JCI73639]