Melanocortin 1 receptor agonists for preventing skin cancer

The melanocortin-1 receptor (MC1R) plays a key role in regulating melanin production, which determines skin pigmentation. Peptide agonists targeting MC1R enhance melanin production, leading to increased pigmentation, and are FDA-approved to treat skin damage caused by porphyria. Unfortunately, the clinical utility of current MC1R peptides is significantly limited by their rapid clearance and cross-reactivity with other receptors within the melanocortin family. Given the role of skin pigmentation in various diseases as well as skin cancer prevention, a selective and potent MC1R agonist could have multiple clinical uses. For example, the ~250,000 solid organ transplant recipients in the USA face a nearly 100-fold increased risk of developing cutaneous squamous cell carcinoma. However, those with increased skin pigmentation are protected. Here, we will create a humanized MC1R agonist antibody with high affinity, potency, and selectivity for the MC1R. We have already rationally designed, humanized, and validated an MC1R agonist antibody fragment with sub-nanomolar potency. We will further affinity mature and optimize the biochemical characteristics of this clone for outlicensing or further internal development. This therapy could have broad clinical applications beyond porphyria, including reducing skin cancer in solid organ transplant recipients, risk reduction for other individuals with skin cancer (> 5 million non-melanoma skin cancers are diagnosed annually in the U.S.), as well as potential cosmetic usage.