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Background:  Chimeric antigen receptor (CAR)-modified T cells have successfully harnessed T cell immunity against malignancies, but they are by no means the only cell therapies in development for cancer.   Main Text Summary:  Systemic immunity is thought to play a key role in combatting neoplastic disease; in this vein, genetic modifications meant to explore other components of T cell immunity are being evaluated. In addition, other immune cells—from both the innate and adaptive compartments—are in various stages of clinical application. In this review, we focus on these non-CAR T cell immunotherapeutic approaches for malignancy. The first section describes engineering T cells to express non-CAR constructs, and the second section describes other gene-modified cells used to target malignancy.   Conclusions:  CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review.

Beyond CAR T Cells: Other Cell-Based Immunotherapeutic Strategies Against Cancer