CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences

Abstract

Chimeric antigen receptor-modified (CAR) T cells targeting CD19 have revolutionized the treatment of relapsed or refractory aggressive B-cell lymphomas, and their use has increased the cure rate for these cancers from 10 to 40%. Two second-generation anti-CD19 CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved for use in patients, and the approval of a third product, lisocabtagene maraleucel, is expected in 2020. The commercial availability of the first two products has facilitated the development of real-world experience in treating relapsed or refractory aggressive B-cell lymphomas, shed light on anti-CD19 CAR T-cell products' feasibility in trial-ineligible patients, and raised the need for strategies to mitigate the adverse effects associated with anti-CD19 CAR T-cell therapy, such as cytokine release syndrome, neurotoxicity, and cytopenia. In addition, promising clinical data supporting the use of anti-CD19 CAR T-cell therapy in patients with indolent B-cell lymphomas or chronic lymphocytic leukemia have recently become available, breaking the paradigm that these conditions are not curable. Multiple clinical CAR T-cell therapy-based trials are ongoing. These include studies comparing CAR T-cell therapy to autologous stem cell transplantation or investigating their use at earlier stages of disease, novel combinations, and novel constructs. Here we provide a thorough review on the use of the anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma or with chronic lymphocytic leukemia, and present novel CAR T cell-based approaches currently under investigation in these disease settings.

Senescent Tumor CD8+ T Cells: Mechanisms of Induction and Challenges to Immunotherapy

“…Currently approved CAR-T cell therapies include the second generation anti-CD19 CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel for the treatment of B-cell malignancies [ 5 , 6 ]. Many more T cell based therapies are currently in the experimental phase of pre-clinical or clinical testing [ 7 ]. While immunotherapies have made remarkable progress in increasing the survival of some patients, low response rates, toxicities, as well as lack of available bio-markers in predicting response, make the successful implementation of these therapies challenging.…”

Co-expression of IL-7 and PH20 Promote anti-GPC3 CAR-T Tumor Suppressor Activity in Vivo and in Vitro

“…3*10 6 CAR-T cells were injected i.v. when the mean tumor volume exceeded 300mm 3 . As shown in Figure 6A, G3CAR-7×20 exhibited a more rapid tumor suppressive activity than did G3CAR.…”

“…W). CAR-T cells were injected intravenously when the tumor volume exceeded 300mm 3 . Body mass was measured every 4 days.…”

“…CAR-T cell therapy has demonstrated encouraging therapeutic effects when treating hematological malignancies [1,2]. Two CAR-T treatments targeting CD19 have been launched successfully [3,4]. CAR-T targeting the B-cell maturation antigen (BCMA) has also shown positive therapeutic effects in clinical trials [5][6][7].…”

Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy

“…CAR T-cell therapy represents the most advanced personalized cancer immunotherapy and has received approval from the FDA and the European Medicine Agency (EMA) for its clinical implementation in the context of hematological cancers, including acute lymphoblastic leukemia and diffuse large Bcell lymphoma (Mohanty et al, 2019;Vitale and Strati, 2020). Thus, CAR T cell therapy is one of the first successful examples of cell engineering and personalized adoptive cell transfer immunotherapy to become available in clinic.…”