Modeling Melanoma Immune Surveillance by CAR-T Cells in Human Skin Organoids.

T cell-mediated therapies are major breakthroughs in the treatment of melanoma. However, clinical hurdles in the application of T cell-mediated therapies in melanoma persist and limit their potential. As such, preclinical research efforts remain focused on their development and optimization. Preclinical research techniques include in vivo evaluation with xenograft mouse models, ex vivo patient tumor explant culture, and in vitro tumor spheroids and melanoma/T cell co-cultures. However, these models lack the appropriate tissue context of melanoma skin cancer. Here, we describe a technique for the incorporation of primary T cells and chimeric antigen receptor (CAR)-T cells with melanoma cells in human skin organoids derived from primary epidermal keratinocytes.