Tumor-associated antigens and neoepitopes (TAA/Neoantigen)

Tumor-associated antigens (TAAs) and neoepitopes (neoantigens) are the fundamental targets for cancer immunotherapy, encompassing a diverse range of molecules recognized by the immune system [ResearchGate]. TAAs are self-antigens that are abnormally expressed in tumor cells, such as overexpressed proteins (e.g., HER2), differentiation antigens (e.g., gp100), or cancer-testis antigens (e.g., NY-ESO-1) [NIH, Crown Bioscience]. In contrast, neoepitopes are entirely novel antigens arising from somatic mutations, such as non-synonymous single nucleotide variants or frameshifts, making them unique to the tumor and highly immunogenic due to the lack of central tolerance [NIH]. These antigens are typically presented as peptides on Major Histocompatibility Complex (MHC) molecules for T-cell recognition, though some TAAs are surface-bound proteins targeted by antibodies [MSD Manuals, Crown Bioscience]. Therapeutic strategies targeting these antigens include cancer vaccines (e.g., mRNA-4157), CAR-T cell therapies (e.g., Tisagenlecleucel), and monoclonal antibodies (e.g., Trastuzumab) [AIM with Immunotherapy, MedChemExpress]. While neoantigens offer superior specificity, TAAs provide shared targets across patient populations, though they carry a higher risk of on-target, off-tumor toxicity and autoimmunity [NIH, BMJ].

Other names

Tumor antigensTumor-specific antigensTSANeoantigensCancer-testis antigensCTAOncofetal antigensDifferentiation antigensCancer-specific neoepitopes

Drugs targeting these antigens primarily function by enhancing the immune system's ability to recognize and eliminate malignant cells. This is achieved through various modalities: therapeutic vaccines (mRNA, DNA, or peptide-based) induce the expansion of antigen-specific T cells; adoptive cell therapies (CAR-T or TCR-T) provide engineered immune cells that directly target the antigens; and monoclonal antibodies or antibody-drug conjugates (ADCs) bind to surface antigens to trigger antibody-dependent cellular cytotoxicity (ADCC) or deliver cytotoxic payloads.