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Patient-specific tumor antigens, commonly referred to as neoantigens, are unique proteins resulting from somatic mutations in a patient's tumor that are absent from healthy tissue (Nature Reviews Cancer, 2017). These antigens are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, allowing the immune system to recognize the tumor as foreign (NCI, 2023). Because they are not expressed in normal cells, they are highly specific targets for immunotherapy, reducing the risk of off-target toxicity and central tolerance (Frontiers in Immunology, 2020). Current therapeutic strategies include personalized mRNA vaccines, such as mRNA-4157, and peptide-based vaccines designed to stimulate a T-cell response against these specific mutations (Science, 2023). Additionally, adoptive cell therapies can be engineered to express T-cell receptors (TCRs) that specifically bind to these patient-specific antigens (Journal of Hematology & Oncology, 2021). While promising, the effectiveness of these therapies depends on the tumor's mutational burden and the accuracy of bioinformatic tools used to predict which mutations will be immunogenic (Nature, 2020).
Induction of a de novo or expanded T-cell mediated immune response specifically targeting unique somatic mutations presented on the surface of tumor cells via MHC molecules (Nature Reviews Cancer, 2017).
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