The Molecular Mechanism Study Of Anti-tumor Effect Of Peptide Vaccine

Cancer is one of the main reasons of death in the most countries.Immunotherapy quickly became one of the best methods of cancer treatment,along with chemotherapy and radiation.Cancer vaccines based on synthetic peptides are a safe,well-tolerated immunotherapy able to specifically stimulate tumor-reactive T cells and elicit an immune response against tumor.Peptide variants are most often selected as vaccine candidates because they bind with stronger affinity or stimulate tumor associated antigen specific T cells more effectively than the native tumor antigen in vitro.Peptide vaccines can expand T cells that naturally respond to tumor antigens,resulting in more effective antitumor immunity.Colon cancer is a world-wide highly prevalent disease and approximately 15% of patients present with a locally advanced tumour.Using the CT26 transplantable tumor model,we showed that vaccination with variants of the immunodominant peptide(AH1),elicited variable antitumor immunity in mouse colon cancer model.The results showed that 60-day survival rate of mice immunized with A5 peptide was 100%,while that of mice immunized with G5 peptide was 25%.Compared with the survival rate of 0 after immunized with AH1 peptide,both A5 and G5 showed obvious immune effects.These peptides robustly stimulated the tumor-specific T cells clone used to identify the peptide variants and elicited more tumor-specific T cells from the endogenous repertoire of BALB/c mice than the native AH1 peptide.We determined the percentage of the specific T cells of AH1 using flow cytometry.A5 peptide could increase 33.7% specific T cells of AH1,and G5 peptide could also increase 9.43% specific T cells of AH1.S5 peptide could increase 2.56% specific T cells of AH1,however,AH1 peptide only increase 0.083% specific T cells of AH1.We also solved the crystal structure of antigen presentation,the complex of the major histocompatibility complex(H2-Ldα1α2)and peptide variant(G5).Compared to the complex of H2-Ld α1α2 and AH1,it is true that the comformation of the main chain of G5 has changed a lot,and those changes may affect the recognition of T cells.From the point of view of function and structure,the structural basis and molecular mechanism of high efficiency peptide vaccines for tumor control were analyzed,which provided some ideas for the future vaccine design.Rationally designed combination therapies are now being tested and should ultimately enable peptide vaccination to be added to cancer treatment options.