Adoptive therapy with CAR redirected T cells for hematological malignancies

Abstract

The survival of patients with hematological malignancies has been significantly improved due to the development of new therapeutic agents. However, relapse remains a major matter for concern. Recently, T cells engineered with chimeric antigen receptor (CAR) were reported to show unprecedented responses in a range of hematological malignancies. The persistence of the CAR-T cell can last for years and tends toward long-term antitumor memory by which relapses can be effectively prevented. The primary side effects that appear in most clinical trials are cytokine release syndrome and neurotoxicity. However, these symptoms can be treated and reversed. In this review, we describe CAR structure and function and summarize recent advances in CAR-T cell therapy in hematological malignancies. cancer, hematological malignancies, immunotherapy, chimeric antigen receptor, T-cell therapy

Genetically enhanced T lymphocytes and the intensive care unit

“…Primary T cells are harvested from a patient’s peripheral blood and enriched. Their enhancement is possible by the use of lentiviral vectors [ 26 - 29 ]. These vectors integrate in the host genome and determine the expression of the CAR construct.…”

Neurotoxicity of Tumor Immunotherapy: The Emergence of Clinical Attention

“…Patients may suffer from headaches during or shortly after the first infusion of cetuximab [ 33 , 35 ], bevacizumab [ 36 ], ipilimumab [ 32 ], rituximab [ 37 ], chimeric antigen receptor T cells (CAR-T) [ 21 ], and pembrolizumab [ 38 ] ( Table 1 ). The symptoms are mostly self-limited, persisting for several days and decreasing soon after finishing the treatment [ 18 , 39 ]. In addition, a headache might also be a manifestation of other complications, such as aseptic meningitis and acute encephalopathy.…”

Genetic engineering of T cells with chimeric antigen receptors for hematological malignancy immunotherapy

“…Zhang et al have found combination of chemotherapy and CAR-T cell exerted better therapeutic effect on solid tumors than CAR-T cell alone (Zhang et al, 2017). There are many potential reasons for these elusive clinical responses, including unmanageable CAR expression in vivo, incompetent trafficking and infiltration of infused cells to tumor sites, lack of CAR-T cell persistence and proliferation, tonic CAR signaling, and the presence of immunosuppressive networks in TME (Adachi et al, 2018b;Beavis et al, 2017;Davenport et al, 2018;Li et al, 2016). In order to take down these obstacles of CAR T-cell therapy, scientists have figured out diverse bioengineering solutions to coordinate with the complex cellular function platform.…”