Novel HLA-A2 restricted antigenic peptide derivatives with high affinity for the treatment of breast cancer expressing NY-ESO-1.

ABSTRACT

Tumor immunotherapy based on specific tumor antigen has become the focus for breast cancer, and research into cancer/testes antigens (CTA) is progressing. As an important member in the CTA, NY-ESO-1 plays a crucial role in the treatment and prognosis of breast cancer. In this study, we aimed to improve the binding ability to MHC by designing and synthesizing stable NY-ESO-1-derived peptides, based on NetMHC 4.0 webserver (http//www.cbs.dtu.dk/services/NetMHC/) and HLP webserver (http//crdd.osdd.net/raghava/hlp/pep_both.htm). Moreover, after modification of the lead compound, affinity of the peptides to human leukocyte antigen-A2 (HLA-A2) was determined by a flow cytometry and an inverted fluorescence microscope in T2 cells that show high expression of HLA-A2. The results demonstrated that the affinity of peptides II-4 and II-10 to HLA-A2 was significantly better when compared to others (II-Lead, II-1 ~ II-3, II-5 ~ II-9, II-11 ~ II-15). Further studies indicated that II-4 and II-10, especially II-4, significantly promoted the maturation of HLA-A2-positive human peripheral blood-derived dendritic cells (DCs) from morphology and surface markers, the activation of CD8 + T lymphocytes, and the type-specific killing effect on HLA-A2+/NY-ESO-1+ MDA-MB-231 cells. Molecular docking studies suggested a strong interaction between peptide II-4 and HLA-A2, thereby indicating that the II-4 is a promising candidate with antigenic potential in the field of immunotherapy that needs more studies.