<p>The increase in cancer incidence and mortality demonstrates the need for more effective anti-tumor therapies. Targeted therapies, such as cancer testicular antigens (CTAs), are promising as they are expressed in tumor cells but not in normal cells. TFDP3, a CTA expressed in cancers such as triple-negative breast cancer, prostate cancer, childhood T-cell lymphoblastic leukemia, and hepatocellular carcinoma, was chosen as a target for vaccine development. This study aimed to predict a multi-epitope vaccine based on TFDP3 using immunoinformatics tools to identify antigenic epitopes that interact with B lymphocytes, CD4+T lymphocytes, and CD8+T lymphocytes. Three epitopes from each lymphocyte type were selected, considering factors such as antigenicity, allergenicity, toxicity, IFN-γ induction, and population coverage. The vaccine also included adjuvants and ligands that ensure the stability and proper processing of the epitopes. The in-silico analysis revealed that the vaccine has favorable physicochemical properties, low homology with human proteins, and interactions with Toll-like receptors, ensuring stability. The population coverage world of the MHC class I and II epitopes were 93.55%. Additionally, the vaccine can be cloned and induce a robust immune response after three administrations. Despite the promising results, immunotherapy still faces challenges, such as tumor heterogeneity and immune evasion. In vitro and in vivo studies are necessary to assess the vaccine’s efficacy and safety for future cancer treatments that express TFDP3.</p>

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In Silico Development of a Multi-epitope Vaccine Targeting TFDP3: A Novel Approach for Cancer Immunotherapy

  • Genilda Castro de Omena Neta,
  • Jose Wilson Batista da Silva Junior,
  • Rodger Marcel Lima Rocha,
  • Ana Kelly da Silva Fernandes Duarte,
  • Emisael Stenio Batista Gomes,
  • Fernando Berton Zanchi,
  • Carolinne de Sales Marques,
  • Carlos Alberto de Carvalho Fraga

摘要

The increase in cancer incidence and mortality demonstrates the need for more effective anti-tumor therapies. Targeted therapies, such as cancer testicular antigens (CTAs), are promising as they are expressed in tumor cells but not in normal cells. TFDP3, a CTA expressed in cancers such as triple-negative breast cancer, prostate cancer, childhood T-cell lymphoblastic leukemia, and hepatocellular carcinoma, was chosen as a target for vaccine development. This study aimed to predict a multi-epitope vaccine based on TFDP3 using immunoinformatics tools to identify antigenic epitopes that interact with B lymphocytes, CD4+T lymphocytes, and CD8+T lymphocytes. Three epitopes from each lymphocyte type were selected, considering factors such as antigenicity, allergenicity, toxicity, IFN-γ induction, and population coverage. The vaccine also included adjuvants and ligands that ensure the stability and proper processing of the epitopes. The in-silico analysis revealed that the vaccine has favorable physicochemical properties, low homology with human proteins, and interactions with Toll-like receptors, ensuring stability. The population coverage world of the MHC class I and II epitopes were 93.55%. Additionally, the vaccine can be cloned and induce a robust immune response after three administrations. Despite the promising results, immunotherapy still faces challenges, such as tumor heterogeneity and immune evasion. In vitro and in vivo studies are necessary to assess the vaccine’s efficacy and safety for future cancer treatments that express TFDP3.