Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine

SHAO Shishuai; DUAN Shukang; TIAN Hong; YAO Wenbing; GAO Xiangdong

doi:10.11665/j.issn.1000-5048.2023022803

Journal of China Pharmaceutical University > 2023 > 54(2): 245-254. > DOI: 10.11665/j.issn.1000-5048.2023022803

SHAO Shishuai, DUAN Shukang, TIAN Hong, YAO Wenbing, GAO Xiangdong. Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine[J]. Journal of China Pharmaceutical University, 2023, 54(2): 245-254. DOI: 10.11665/j.issn.1000-5048.2023022803

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Design and antitumor activity of programmed cell death ligand 1 epitope peptide vaccine

Jiangsu Provincial Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the National Natural Science Foundation of China (No.82073754, No.81973222); and the Key Research and Development Program of Xinjiang Uygur Autonomous Region (No.2020B03003)

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Received Date: February 27, 2023
Revised Date: April 02, 2023

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Abstract

Abstract

Several programmed cell death protein 1 (PD-1) or its ligand (PD-L1) immune checkpoint blocking antibodies are available for clinical treatment, but only some patients show clinical response, so an alternative strategy for tumor immunotherapy is needed.A therapeutic tumor vaccine targeting PD-L1 is a meaningful attempt.In this study, we designed an epitope peptide vaccine targeting PD-L1, and then screened the immunogenic PD-L1 epitope peptide based on the humanized immune system (HIS) mouse model and further investigated its anti-tumor activity.The results show that the designed and screened PD-L1-B1 epitope peptide vaccine not only successfully induced PD-L1-specific humoral and cellular immunity, but also exhibit anti-tumor activity.In addition, immunotherapy increased T-lymphocyte infiltration of tumors and reshaped the tumor immunosuppressive microenvironment.In conclusion, PD-L1-B1 epitope peptide vaccine exhibits potent anti-tumor activity and may be an effective alternative immunotherapeutic strategy for patients insensitive to PD-1/PD-L1 blockade.
- tumor immunity,
- immune checkpoint,
- PD-L1,
- epitope peptide vaccine

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[1]	Morad G, Helmink BA, Sharma P, et al. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade[J]. Cell, 2022, 185(3): 576.
[2]	Zhou F, Qiao M, Zhou CC. The cutting-edge progress of immune-checkpoint blockade in lung cancer[J]. Cell Mol Immunol, 2021, 18(2): 279-293.
[3]	André; T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer[J]. N Engl J Med, 2020, 383(23): 2207-2218.
[4]	Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial[J]. Lancet, 2021, 398(10294): 27-40.
[5]	Doroshow DB, Sanmamed MF, Hastings K, et al. Immunotherapy in non-small cell lung cancer: facts and hopes[J]. Clin Cancer Res, 2019, 25(15): 4592-4602.
[6]	Huang AC, Zappasodi R. A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance[J]. Nat Immunol, 2022, 23(5): 660-670.
[7]	Lei QY, Wang D, Sun K, et al. Resistance mechanisms of anti-PD-1/PD-L1 therapy in solid tumors[J]. Front Cell Dev Biol, 2020, 8: 672.
[8]	Tian H, Kang YL, Song XD, et al. PD-L1-targeted vaccine exhibits potent antitumor activity by simultaneously blocking PD-1/PD-L1 pathway and activating PD-L1-specific immune responses[J]. Cancer Lett, 2020, 476: 170-182.
[9]	Liu YT, Sun ZJ. Turning cold tumors into hot tumors by improving T-cell infiltration[J]. Theranostics, 2021, 11(11): 5365-5386.
[10]	Bruni D, Angell HK, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy[J]. Nat Rev Cancer, 2020, 20(11): 662-680.
[11]	McAuliffe J, Chan HF, Noblecourt L, et al. Heterologous prime-boost vaccination targeting MAGE-type antigens promotes tumor T-cell infiltration and improves checkpoint blockade therapy[J]. J Immunother Cancer, 2021, 9(9): e003218.
[12]	Blass E, Ott PA. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines[J]. Nat Rev Clin Oncol, 2021, 18(4): 215-229.
[13]	Ott PA, Hu-Lieskovan S, Chmielowski B, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer[J]. Cell, 2020, 183(2): 347-362.e24.
[14]	Parkhurst MR, Robbins PF, Tran E, et al. Unique neoantigens arise from somatic mutations in patients with gastrointestinal cancers[J]. Cancer Discov, 2019, 9(8): 1022-1035.
[15]	Geuijen C, Tacken P, Wang LC, et al. A human CD137 × PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade[J]. Nat Commun, 2021, 12(1): 4445.
[16]	Munir S, Lundsager MT, J?rgensen MA, et al. Inflammation induced PD-L1-specific T cells[J]. Cell Stress, 2019, 3(10): 319-327.
[17]	Daassi D, Mahoney KM, Freeman GJ. The importance of exosomal PD-L1 in tumour immune evasion[J]. Nat Rev Immunol, 2020, 20(4): 209-215.
[18]	Guo LL, Overholser J, Good AJ, et al. Preclinical studies of a novel human PD-1 B-Cell peptide cancer vaccine PD-1-Vaxx from BALB/c mice to beagle dogs and to non-human primates (Cynomolgus monkeys)[J]. Front Oncol, 2022, 12: 826566.
[19]	Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade[J]. Science, 2018, 359(6382): 1350-1355.
[20]	Yu W, Jiang N, Ebert PJ, et al. Clonal deletion prunes but does not eliminate self-specific αβ CD8⁺ T lymphocytes[J]. Immunity, 2015, 42(5): 929-941.
[21]	Tian H, He Y, Song XD, et al. Nitrated T helper cell epitopes enhance the immunogenicity of HER2 vaccine and induce anti-tumor immunity[J]. Cancer Lett, 2018, 430: 79–87.
[22]	Su S, Zou ZY, Chen FJ, et al. CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer[J]. Oncoimmunology, 2017, 6(1): e1249558.
[23]	Nelde A, Rammensee HG, Walz JS. The peptide vaccine of the future[J]. Mol Cell Proteomics, 2021, 20: 100022.
[24]	Liao P, Wang WM, Wang WC, et al. CD8⁺ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4[J]. Cancer Cell, 2022, 40(4): 365-378.e6.
[25]	Gao Y, Yang JJ, Cai YX, et al. IFN-γ-mediated inhibition of lung cancer correlates with PD-L1 expression and is regulated by PI3K-AKT signaling[J]. Int J Cancer, 2018, 143(4): 931-943.
[26]	Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy[J]. Nat Rev Immunol, 2018, 18(10): 648-659.
[27]	Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition[J]. Clin Cancer Res, 2016, 22(8): 1865-1874.

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