Synthetic tumor-specific antigenic peptides with a strong affinity to HLA-A2 elicit anti-breast cancer immune response through activating CD8+ T cells

Researches on tumor-associated antigen have become a hoi target in immunotherapy, but it stagnated in the pre-clinical/clinical stages. Here, we developed a series of MAGE-A1-restricted antigenic peptides, which exhibited prominent inhibiting effect on specific breast cancer. Peptides were synthesized by Fmoc solid phase method and analyzed by online servers. The stability and affinity to HLA-A2 was assessed by inverted fluorescence and flow cytometry qualitatively and quantitatively. In vitro effect on dendritic cells (DCs) maturation was observed by morphology and surface markers. The secretion of IFNy in the supernatant was detected by co-incubation of DCs loaded with as-synthesized peptides and CD8(+) T lymphocytes. The specific immune response was evaluated against 4 cell lines, and the response in MCF-7 xenografted BALB/c nude mice were further assessed. Most of the derived peptides, especially 16, showed great HLA-A2 binding ability. Compared with cytokines, 1-6 significantly induced DCs maturation and promoted CD8(+) T lymphocytes activation. Additionally, it is more specific for the lethality of MAGE & HLA-A2 double positive cells compared with others. We successfully developed 1-6 with a high affinity to HLA-A2 which could induce strong specific immune response. It could be a potential candidate for breast cancer immunotherapy, which deserves further studies. (C) 2020 Elsevier Masson SAS. All rights reserved.