Citation: | ZHOU Hongyou, GAO Xiangdong, YAO Wenbing, et al. Screening of adjuvant for PD-L1 vaccine based on nitrated T cell epitope[J]. J China Pharm Univ, 2024, 55(3): 397 − 403. DOI: 10.11665/j.issn.1000-5048.2023032801 |
To enhance the anti-tumor activity of tumor vaccine targeting PD-L1 based on the nitrated T-epitope (PD-L1-NitraTh), this research compared several adjuvants with different mechanisms to screen out the adjuvant most suitable for PD-L1-NitraTh. The results showed that Poly(I:C), CPG1018, swollen knotted polysaccharide SGP2 and GM-CSF could enhance the immunogenicity of PD-L1-NitraTh when used as adjuvants, with the Poly(I:C) group inducing the highest antibody titer. The results of qPCR for T cell differentiation-related cytokines showed that Poly(I:C) reduced the expression of GATA3 and FoxP3, indicating a strong effect on CD4+ T cell differentiation. Besides, compared with other adjuvants, Poly(I:C) could assist PD-L1-NitraTh to increase the infiltration of T cells as well as CD11b+ cells within tumor, suggesting that Poly(I:C) may be the suitable adjuvant for tumor vaccines based on the nitrated T epitopes.
[1] |
Igarashi Y, Sasada T. Cancer vaccines: toward the next breakthrough in cancer immunotherapy[J]. J Immunol Res, 2020, 2020: 5825401.
|
[2] |
Christofi T, Baritaki S, Falzone L, et al. Current perspectives in cancer immunotherapy[J]. Cancers, 2019, 11(10): 1472.
|
[3] |
Solinas C, Aiello M, Migliori E, et al. Breast cancer vaccines: Heeding the lessons of the past to guide a path forward[J]. Cancer Treat Rev, 2020, 84: 101947.
|
[4] |
Liu WS, Tang HC, Li LF, et al. Peptide-based therapeutic cancer vaccine: current trends in clinical application[J]. Cell Prolif, 2021, 54(5): e13025.
|
[5] |
He Q, Gao H, Gao M, et al. Immunogenicity and safety of a novel tetanus toxoid-conjugated anti-gastrin vaccine in BALB/c mice[J]. Vaccine, 2018, 36(6): 847-852.
|
[6] |
Pulendran B, Arunachalam PS, O’Hagan DT. Emerging concepts in the science of vaccine adjuvants[J]. Nat Rev Drug Discov, 2021, 20(6): 454-475.
|
[7] |
Petrovsky N. Comparative safety of vaccine adjuvants: a summary of current evidence and future needs[J]. Drug Saf, 2015, 38(11): 1059-1074.
|
[8] |
Cohet C, van der Most R, Bauchau V, et al. Safety of AS03-adjuvanted influenza vaccines: a review of the evidence[J]. Vaccine, 2019, 37(23): 3006-3021.
|
[9] |
Alving CR, Beck Z, Matyas GR, et al. Liposomal adjuvants for human vaccines[J]. Expert Opin Drug Deliv, 2016, 13(6): 807-816.
|
[10] |
Ma XL, Kadir Z, Li JY, et al. The effects of GM-CSF and IL-5 as molecular adjuvants on immune responses and contraception induced by mZP3 DNA vaccination[J]. Am J Reprod Immunol, 2012, 68(6): 476-485.
|
[11] |
Jackson S, Lentino J, Kopp J, et al. Immunogenicity of a two-dose investigational hepatitis B vaccine, HBsAg-1018, using a toll-like receptor 9 agonist adjuvant compared with a licensed hepatitis B vaccine in adults[J]. Vaccine, 2018, 36(5): 668-674.
|
[12] |
Stewart E, Triccas JA, Petrovsky N. Adjuvant strategies for more effective tuberculosis vaccine immunity[J]. Microorganisms, 2019, 7(8): 255.
|
[13] |
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.
|
[14] |
Tian H, Kang YL, Song XD, et al. PDL1-targeted vaccine exhibits potent antitumor activity by simultaneously blocking PD1/PDL1 pathway and activating PDL1-specific immune responses[J]. Cancer Lett, 2020, 476: 170-182.
|
[15] |
Yu F, Sharma S, Edwards J, et al. Dynamic expression of transcription factors T-bet and GATA-3 by regulatory T cells maintains immunotolerance[J]. Nat Immunol, 2015, 16(2): 197-206.
|
[16] |
Uematsu S, Akira S. Toll-like receptors and type I interferons[J]. J Biol Chem, 2007, 282(21): 15319-15323.
|
[17] |
Lu FJ, Mosley YC, Carmichael B, et al. Formulation of aluminum hydroxide adjuvant with TLR agonists poly(I: C) and CpG enhances the magnitude and avidity of the humoral immune response[J]. Vaccine, 2019, 37(14): 1945-1953.
|
[18] |
Jack CS, Arbour N, Blain M, et al. Th1 polarization of CD4+ T cells by Toll-like receptor 3-activated human microglia[J]. J Neuropathol Exp Neurol, 2007, 66(9): 848-859.
|
[19] |
Ko KH, Cha SB, Lee SH, et al. A novel defined TLR3 agonist as an effective vaccine adjuvant[J]. Front Immunol, 2023, 14: 1075291.
|
[20] |
Apostólico JS, Lunardelli VAS, Yamamoto MM, et al. Poly(I: C) potentiates T cell immunity to a dendritic cell targeted HIV-multiepitope vaccine[J]. Front Immunol, 2019, 10: 843.
|
[21] |
Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis[J]. Cancer Res, 2012, 72(9): 2162-2171.
|
[22] |
Seya T, Matsumoto M. The extrinsic RNA-sensing pathway for adjuvant immunotherapy of cancer[J]. Cancer Immunol Immunother, 2009, 58(8): 1175-1184.
|
[23] |
Schmid MC, Khan SQ, Kaneda MM, et al. Integrin CD11b activation drives anti-tumor innate immunity[J]. Nat Commun, 2018, 9(1): 5379.
|