Cystine degradation boosts immunotherapies in melanoma

INDICATION: Melanoma

Patient sample and mouse studies suggest promoting ferroptosis by degrading cystine could enhance the efficacy of anti-PD-1 immunotherapies in melanoma. In melanoma patients, high tumor levels of SLC7A11 and SLC3A2, which transport the ferroptosis inhibitor cystine into cells, were associated with low tumor numbers of CD8+ T cells and poor survival. In a mouse model of melanoma, the dual cystine/cysteine-degrading enzyme AECase plus an anti-PD-L1 mAb increased numbers of CD8+ and CD4+ T cells in tumors and decreased tumor size compared with either agent alone. Next steps could include testing AECase in combination with other immunotherapies in models of melanoma...