Definition: A neoantigen is a novel protein fragment that arises from tumor-specific mutations and is presented on cancer cell surfaces by MHC molecules. Unlike normal cellular antigens, neoantigens result from genetic alterations unique to each tumor, such as point mutations or chromosomal rearrangements. Since these peptides are absent in healthy tissues, they represent truly foreign targets that the immune system can recognize without risking autoimmune reactions against normal cells.

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In personalized cancer vaccines, neoantigens serve as patient-specific targets tailored to each individual's unique tumor mutational profile. The approach involves sequencing the patient's tumor to identify mutations, computationally predicting which mutated peptides will be presented by the patient's MHC molecules, and incorporating these predicted neoantigens into vaccine formulations. This personalized strategy aims to stimulate targeted immune responses against the patient's specific cancer while avoiding the limitations of traditional vaccines that target shared tumor antigens.