CAR T Cell Therapy for Chronic Lymphocytic Leukemia: Successes and Shortcomings

Abstract

Chimeric antigen receptor T (CAR T) cell therapy achieved remarkable success in B-cell leukemia and lymphoma which led to its incorporation in treatment protocols for these diseases. CAR T cell therapy for chronic lymphocytic leukemia (CLL) patients showed less success compared to other malignant tumors. In this review, we discuss the published results regarding CAR T cell therapy of CLL, possible mechanisms of failures and expected developments.

Keywords: CAR NK cells; CAR T cells; CLL.

Figure 1

The process of autologous CAR T cell therapy. T cells are collected via apheresis, genetically reengineered in a laboratory by introducing DNA that encodes CAR, multiplied, and then infused into the patient. The CAR T cells may eliminate all of the cancer cells and may remain in the body months after the infusion.

Figure 2

Challenges in CAR T-cell therapy. The first problem associated with CAR T cell therapy is access which can be limited by the cost of the manufacture of CAR T cells, time needed to manufacture and expand CAR T cells, failure to produce autologous CAR T cells, and eligibility for the clinical trial. The second problem associated with CAR T cell therapy are serious adverse event: cytokine-release storm (widespread pyroptosis of tumor cells is followed by the release of different factors that activate macrophages to produce inflammatory cytokines that induce systemic inflammatory response), and neurotoxicity syndrome (toxic encephalopathy caused by the disruption of the blood-brain-barrier). CAR T cell therapy may be accompanied by the primary resistance due to the impaired CAR T cell function and the inability to induce remission and limited CAR T cell expansion.

Figure 3

Novel attempts to improve CAR T cell therapy in CLL.