Chimeric Antigen Receptor T-Cell Therapy: What We Expect Soon

Abstract

The treatment landscape for hematologic malignancies has changed since the recent approval of highly effective chimeric antigen receptor T-cell therapies (CAR-T). Moreover, more than 600 active trials are currently ongoing. However, early enthusiasm should be tempered since several issues are still unsolved and represent the challenges for the coming years. The lack of initial responses and early relapse are some hurdles to be tackled. Moreover, new strategies are needed to increase the safety profile or shorten the manufacturing process during CAR-T cells therapy production. Nowadays, most clinically evaluated CAR-T cells products are derived from autologous immune cells. The use of allogeneic CAR-T cells products generated using cells from healthy donors has the potential to change the scenario and overcome many of these limitations. In addition, CAR-T cells carry a high price tag, and there is an urgent need to understand how to pay for these therapies as many of today’s current payment systems do not feature the functionality to address the reimbursement gap. Finally, the clinical experience with CAR-T cells for solid tumors has been less encouraging, and development in this setting is desirable.

Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors

“…To date, compared with haematological neoplasms, the road to using CAR-T cell therapy approach in solid tumors is much more complex; this is due to various problems, the most important being intra-tumor heterogeneity and TME-mediated protumoral activity ( 99 ). Indeed, no CAR-T cell therapy is approved in solid tumors.…”

CAR T-Cell Persistence Correlates with Improved Outcome in Patients with B-Cell Lymphoma

“…For patients with relapsed/refractory (r/r) disease, the development and approval of CD19-targeting chimeric antigen receptor (CAR) T-cell therapies has supposed a revolutionary treatment opportunity [ 1 , 2 , 6 ]. CAR T-cell therapies rely on genetic engineering of patient-derived T-cells [ 7 , 8 , 9 ]. These T-cells are collected from peripheral blood (PB), and in vitro modified to successfully bind specific tumor cell surface antigens, triggering potent antitumor responses [ 7 , 9 ].…”

“…For treatment of B-cell malignancies, currently approved and commercially available CAR T-cell products target the B-cell surface antigen CD19 [ 13 , 14 ]. Three CAR T-cell products, tisagenlecleucel (Kymriah ® ), axicabtagene ciloleucel (Yescarta ® ) and lisocabtagene maraleucel (Breyanzi ® ), are FDA approved for patients with diffuse large B-cell lymphoma (DLBCL), r/r after two or more systemic treatment lines [ 2 , 7 , 8 , 15 ]. Tisagenlecleucel is also authorized for patients under 25 years diagnosed with r/r B-cell acute lymphoblastic leukemia (B-ALL) [ 7 ].…”

“…These therapies have lead to unprecedentedly high rates of tumor responses and durable disease remissions. For instance, axicabtagene ciloleucel showed in the ZUMA-1 trial an objective response rate as high as 82%, with a complete response rate of 54%, in patients with r/r DLBCL, transformed FL and primary mediastinal B-cell lymphoma [ 8 , 13 , 16 ]. Furthermore, CAR T-cell therapy has shown outstanding success in patients with B-ALL, with complete response rates between 70% and 94% across distinct trials [ 13 ].…”

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms?

“…Second- and third-generation CAR-T cells have an additional costimulatory intracellular domain (e.g., CD28, 41BB, OX40) that enhances the CAR-T cells’ ability to proliferate, expand, and persist in vivo ( Figure 1 ). However, new strategies are needed to increase the safety profile and shorten the manufacturing process during CAR-T cells therapy production [ 15 ].…”