Targeting melanoma growth with CAR DCs
Minnee J, Wong WZH, Russell BS, et al. Chimeric Antigen Receptor Dendritic Cells Suppress Melanoma Growth in Preclinical Cancer Models. Journal for ImmunoTherapy of Cancer. 2025; 13 (12) (doi: 10.1136/jitc-2025-013040).
Chimeric antigen receptor (CAR) T-cell therapy has not achieved the same level of success with solid tumors as it has with hematological cancers, but results of a preclinical experiment suggest that adding CAR to dendritic cells (DCs) is an alternative strategy worth exploring further. DCs are professional antigen-presenting cells and professional phagocytes with the potential to overcome challenges presented by the immunosuppressive tumor microenvironments (TMEs) that characterize solid tumors. Researchers tested the concept in a murine melanoma model in which DCs were enhanced with an anti-human epidermal growth factor receptor 2 (HER2) CAR. The cells suppressed the growth of B16.HER2 tumors, although the independent effect was modest. Potency of antitumor activity was improved via introduction of CD40L — a cell-surface receptor that stimulates DC maturation and Th1 cytokine secretion and also induces the CD83 and CD86 proteins that increase DCs' ability to activate T cells — to the CAR vector. Incorporating a vector-expressed PD-1-based checkpoint inhibitor, which reversed T-cell exhaustion and amplified the antitumor response, and adding a GM-CSF gene to the vector increased CAR-DC potency and durability even further.