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Melanoma-specific antigens (MSAs), also known as melanoma-associated antigens (MAAs), represent a heterogeneous group of proteins that are either exclusively or preferentially expressed in melanoma cells compared to normal tissues [5, 22]. This broad category includes cancer-testis antigens (e.g., MAGE family, NY-ESO-1), which are silent in normal adult tissues except for germ cells; melanocyte differentiation antigens (e.g., gp100, MART-1, tyrosinase), which are involved in melanin synthesis; and overexpressed surface antigens like HMW-MAA (CSPG4) [9, 15, 20]. These antigens serve as critical targets for various immunotherapeutic strategies, including cancer vaccines, T-cell receptor (TCR) engineered T-cells, and bispecific T-cell engagers (BiTEs) [4, 8, 10]. While differentiation antigens are expressed in both malignant and normal melanocytes, leading to potential off-target effects like vitiligo, cancer-testis antigens offer higher tumor specificity [11, 17]. Despite their promise, many MSA-targeted vaccines have faced challenges in clinical trials, though newer modalities like the gp100-targeting bispecific tebentafusp have demonstrated significant clinical benefit in specific patient populations [16, 24].
T-cell engagement, Active immunization, Adoptive cell transfer
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