The Promise of Chimeric Antigen Receptor Engineered T Cells in the Treatment of Hematologic Malignancies

Abstract

Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) have shown high complete response rates in patients with few therapeutic options. Exploration is ongoing for other hematologic malignancies including multiple myeloma (MM), acute myeloid leukemia (AML) and Hodgkin lymphoma (HL). At the same time, the design and production of CAR T cells is being advanced so that this therapy can be more widely utilized. Cytokine release syndrome (CRS) and neurotoxicity are common, but they are treatable and fully reversible. This review will review currently available data as well as future developments and challenges in the field.

Dendritic Cell Therapies for Hematologic Malignancies

“…Combining vaccination with immunomodulatory drugs such as lenalidomide or immune checkpoint blockade is being explored. 91 , 92 Future research efforts in this realm are also likely to include exploration of combinations of DC-tumor vaccination with various novel immunotherapy strategies, including chimeric antigen receptor (CAR) T lymphocyte therapy, 93 myeloid-derived suppressor cell (MDSC) inhibitors, 94 and therapies that deplete Tregs, 95 as well as lentviral or retroviral gene therapy techniques for improved induction of anti-tumor immune response. 96 , 97 …”

Neurotoxicity of Tumor Immunotherapy: The Emergence of Clinical Attention

“…This process is called CRS [ 104 , 105 ]. Although recent research shows that the neurologic ir-AEs are irrelevant to CRS, there is evidence that patients who undergo CRS after immunotherapy are more vulnerable to developing neurologic ir-AEs [ 13 , 106 ]. Studies have demonstrated that neurologic ir-AEs secondary to CAR-T therapy is probably related to the markedly elevated inflammatory cytokines, such as IL-6, IL-2, interferon- γ , and TNF- α [ 16 , 102 , 107 , 108 ].…”

Therapeutic dendritic cell cancer vaccines in hematologic malignancies

“…Preclinical studies combining CAR T cell therapy with vaccination have also demonstrated potential activity 103,104 . In animal models, our group has examined the capacity of the DC/tumor vaccine to enhance CAR T cell activity potentially through the broadening of the antitumor T cell response via the native TCR and the cyclic re‐expansion and activation of the CAR population via vaccine‐mediated stimulation 105 …”