Melanoma, the most dangerous form of skin cancer that kills approximately 9,320 Americans annually, arises when pigment-producing melanocytes mutate and form malignant tumors. The main cause of melanoma is due to occasional, intense UV exposure. Incidence of melanoma has been on the rise in people under the age of 40, especially in women. If melanoma is not treated adequately in the early stage, the cancer can progress and spread or metastasize.
The breakthrough of immunotherapy has shed light on cancer treatment. However, new strategies still need to be further explored and improved to benefit the patients. Deficiency of tumor-reactive T cells brings a major challenge to current immune checkpoint inhibitor immunotherapies. Potentially, a vaccination that induces melanoma-specific T cells could play a significant role in enhancing the efficacy of immune checkpoint inhibitors in skin cancer, by effectively destroying the tumor’s local tolerogenic mechanisms and thereby killing the tumor cells.
A recent study done by Dinther et al. explored a peptide vaccination strategy by conjugation to anti-CD169 antibodies (Abs), which stimulated strong melanoma antigen-specific T cell responses in both mice and humans. Splenic macrophages that express CD169 sialic acid receptors capture the bloodstream antigen and transfer it to dendritic cells. Immunization using gp100, Trp-2 and MART-1 peptides conjugated to CD169 Abs induced strong melanoma-specific T cell responses, which is potentially a powerful strategy for next-generation peptide-based immunotherapy in skin cancer treatment. Furthermore, vaccination with CD169-specific Abs conjugated to recently-identified personalized neo-antigen (neo-Ag) peptides may also be used to convince stronger clinical significance.
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