Clinical and functional profiling nominates melanoma as a priority indication for GPNMB CAR T cell therapy

GPNMB-high models were efficiently eliminated, antigen-low models showed intermediate susceptibility, and antigen-negative models showed no antitumor activity. Melanoma profiling demonstrated the most favorable clinical expression profile. Analysis of 158 patients revealed frequent, high GPNMB expression across anatomically diverse primary tumors and metastatic specimens.

Spatial transcriptomic analysis further corroborated that GPNMB was most frequently detected in malignant-cell-dominant regions. Consistent with this clinical profile, GPNMB CAR T cells demonstrated activity across a diverse panel of melanoma cell models. Together, these findings support GPNMB as a broadly relevant but variably expressed tumor antigen and nominate melanoma as a priority clinical entry point for GPNMB CAR T cell therapy.