Immunologic treatment strategies in mantle cell lymphoma: checkpoint inhibitors, chimeric antigen receptor (CAR) T-cells, and bispecific T-cell engager (BiTE) molecules

Over the past 10–15 years, there has been a surge in the development and utilization of immunologic strategies aimed at harnessing the power of the cellular immune system to treat a remarkable range of human disease. As is being seen throughout the spectrum of malignant hematology, there are several emerging immunologic therapies which may ultimately revolutionize the treatment and clinical outcomes of patients with mantle cell lymphoma (MCL). Three unique immunologic approaches—checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific T-cell engager (BiTE) molecules—are currently on the forefront of clinical investigation. While preclinical studies have suggested a mechanistic role for immunomodulation via checkpoint blockade (PD-L1, PD-1) in patients with MCL, clinical data thus far suggests only modest success. CAR T-cell therapies, engineered to directly overcome deficiencies in the anti-tumor T-cell response, appear to show early promise and large trials actively enrolling MCL patients are currently in progress. BiTE molecules, which seek to engage and directly activate the cytotoxic power of T-cells upon bispecific interaction with tumor antigen, are being explored in treatment of MCL and early efficacy data seems encouraging as well.