Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T

Abstract In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies in most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure of CAR-T and immune checkpoint blockade in several solid neoplasms is attributed to multiple factors, including low antigenicity of tumor cells, low infiltration of effector T cells, and diverse mechanisms of immunosuppression in the tumor microenvironment. New adoptive cell therapies have been attempted for solid neoplasms, including TCR-T, CAR-natural killer cells (CAR-NK), and CAR-macrophages (CAR-M). Compared to CAR-T, these new adoptive cell therapies have certain advantages in treating solid neoplasms. In this review, we summarized the 40-year evolution of adoptive cell therapies, then focused on the advances of TCR-T, CAR-NK, and CAR-M in solid neoplasms and discussed their potential clinical applications.