Tumor Antigens Introduction Tumor antigens are molecules expressed on the surface of tumor cells that can trigger an immune response. These antigens play a crucial role in the detection and destruction of cancer cells by the immune system. Understanding tumor antigens is essential for developing effective cancer immunotherapies, such as cancer vaccines and adoptive T cell therapies. Types of Tumor Antigens 1. Tumor-Specific Antigens (TSAs) o o Definition: TSAs are unique to tumor cells and are not present on normal cells. They arise from mutations in the DNA of tumor cells. Examples: ▪ Neoantigens: These are new antigens generated from somatic mutations in tumor cells. For example, mutations in KRAS or BRAF can produce neoantigens that are recognized as foreign by the immune system. ▪ Oncogenic Mutations: Mutations in oncogenes like EGFR or tumor suppressor genes like p53 can lead to the production of abnormal proteins that serve as TSAs. 2. Tumor-Associated Antigens (TAAs) o o Definition: TAAs are expressed on both tumor and normal cells but are overexpressed or aberrantly expressed in tumors. Examples: ▪ Cancer-Testis Antigens: These antigens are normally restricted to testicular tissue but are aberrantly expressed in various tumors. Examples include NYESO-1 and MAGE-A1. ▪ Differentiation Antigens: These are expressed during normal cell differentiation but are re-expressed or overexpressed in tumors. Examples include CEA (Carcinoembryonic Antigen) and HER2/neu (Human Epidermal Growth Factor Receptor 2). Immune Response to Tumor Antigens 1. Antigen Presentation o MHC Molecules: Tumor antigens are processed and presented by Major Histocompatibility Complex (MHC) molecules to T cells. TSAs are typically presented by MHC class I molecules to CD8+ cytotoxic T cells, while TAAs may be presented by both MHC class I and class II molecules. 2. T Cell Activation o o CD8+ Cytotoxic T Cells: These cells recognize and kill tumor cells presenting specific tumor antigens. CD4+ Helper T Cells: These cells help coordinate the immune response by releasing cytokines that support other immune cells. 3. Antibody Production o B Cells: B cells can produce antibodies against tumor antigens. Monoclonal antibodies, such as trastuzumab for HER2+ breast cancer, are used therapeutically to target tumor cells. Tumor Antigen-Based Therapies 1. Cancer Vaccines o o Preventive Vaccines: Designed to prevent cancer in high-risk individuals. For example, the HPV vaccine prevents cervical cancer by targeting HPV antigens. Therapeutic Vaccines: Aim to treat existing cancer by stimulating the immune system against tumor antigens. Examples include the Sipuleucel-T vaccine for prostate cancer. 2. Adoptive T Cell Therapy o CAR-T Cell Therapy: Involves engineering T cells to express chimeric antigen receptors (CARs) targeting specific tumor antigens, such as CD19 in B-cell malignancies. Challenges and Future Directions • • Antigen Escape: Tumor cells may lose the expression of tumor antigens or alter antigen presentation mechanisms to evade immune detection. Immune Suppression: Tumors can create an immunosuppressive microenvironment that hinders the effectiveness of immune responses against tumor antigens. Future research aims to identify novel tumor antigens, improve vaccine designs, and develop strategies to overcome antigen escape and immune suppression.