Abstract LB051: The landscape of peptide vaccinein clinical trials for cancer

Abstract

Background: For an anticancer immune response to lead to the effective killing of cancer cells, a key determinant is selecting suitable immunogenic tumor antigens as the immunotherapy targets. Recent studies have highlighted the relevance of tumor-associated antigens encoded by amino acid substitutions (AASs) in recognition of cancer cells by the immune system. This has prompted the development of personalized vaccines and cell therapies targeting cancer mutations. Recently immunotherapy has been merged as a promising new treatment method for cancer due to its remarkable anti-tumor efficacy and low side effects. One of the key factors limiting the application of immunotherapy is the lack of suitable tumor antigens. Our work aims to investigate what kinds of tumor antigens and treatment conditions can help obtain satisfactory clinical treatment results.Finding: We collected tumor-associated antigens of clinical tumor peptide vaccine therapy from different databases and constructed a tumor antigens library. Candidate tumor peptides can activate T cells to release IFN-ϒ and have high cytotoxicity for tumor cells. They could be used as peptide vaccines or as targets for adoptive cell therapy (DC cells, CTL cells, TCR-T cells, CART cells). To find the causes which influence peptide vaccine treatment effect. Several significant factors, including peptide antigens, peptide types, adjuvants, and treatment strategy, were analyzed in response results and no response results. We found that most peptides, which were used in clinical cases, are an expression or high expression. There are more overexpression peptides than other types of peptides ineffective results of colorectal (P=0.0002). But fusion peptide vaccines have no advantages in cancer peptide vaccine therapy. Modify or high expression peptides could be suitable alternative peptides for peptide vaccine in cancer immunotherapy, especially melanoma immunotherapy. Although the SNV peptides have no significant therapeutic advantages in non-individualized vaccine therapy, tumor neo-antigen peptides maybe have significant benefits in individualized vaccine therapy. GM-CSF and ISA-51 are the two most common adjuvants, and IL-4, IL-4, IL-12 are the main cytokines and additives in response results, especially in breast cancer and melanoma. But most cases did not use any adjuvants in peptide vaccine preparation.We also found that PMEL, MAGE-1,4,3,6, SART3, LCK, TP53, CEA, and ERBB2 are the top 8 antigens of clinical phase peptides. The antigens of response peptides are also significant differences in different cancers. Treatment strategy also plays a vital role in the therapeutic efficacy of peptide vaccine. The interval of 1-2 weeks and more than 4 times vaccine could be the typical treatment strategy for response clinical trials.Conclusions: Peptide vaccines provide apparent advantages in comparison to traditional therapies. Peptide vaccine production is relatively inexpensive due to the ease of production and simplistic composition. Moreover, peptide vaccines can be composed of various epitopes from different antigens and integrate T cell and B cell epitopes into one antigenic formulation. It is crucial to choose suitable peptide antigens and treatment conditions for cancer vaccine therapy.Keywords: Peptide vaccine; Clinical trials; Cancer; Phase- 1 - Citation Format: Chongming Jiang, Geng Liu, Wei Zhang, Zhenkun Zhuang, Wenhui Li, Si Qiu, Cheng-chi Chao, Bo Li, Chao Cheng. The landscape of peptide vaccinein clinical trials for cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB051.