Abstract
Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.
Highlights
For decades the only available cancer treatments were surgical resection as well as chemotherapy and/or radiotherapy [1]
Latter can consist of different molecules, such as nanobodies, designed ankyrin repeat proteins (DARPins), Fig. 1 Schematic illustration of a Chimeric antigen receptor (CAR)-T or CAR-natural killer (NK) cell therapy, which uses primary immune cells
CAR-T cells have shown astonishing results in the treatment of mostly relapsed or refractory (r/r) hematological malignancies, which have already resulted in the approval of three drugs by the U.S Food and Drug Administration (FDA) and the European Commission (EC) between 2017 and beginning of 2021 [15–17]
Summary
CD19-CAR-T cell products 2018-000973-57(o) (NCT03630159) 2017-002116-14 (NCT03876769) 2017-004385-94 (NCT03568461) 2013-003205-25 (NCT02435849) 2014-003060-20 (NCT02445248) 2016-002966-29 (NCT03570892) 2016-001991-31 (NCT03123939) 2015-005007-86 (NCT02348216) 2017-002261-22 (NCT03391466) 2015-005010-30 (NCT02625480) 2018-001923-38 (NCT03624036) 2015-005009-35 (NCT02614066) 2015-005008-27 (NCT02601313) 2018-001246-34 (NCT03743246) 2019-004081-18(o) (NCT04245839). Phase Ib study of tisagenlecleucel in combination with pembrolizumab in r/r diffuse large B-cell lymphoma (DLBCL) patients (PORTIA). A phase II, single arm, multicenter open-label trial to determine the efficacy and safety of tisagenlecleucel (CTL019) in adult patients with refractory or relapsed follicular lymphoma (ELARA). A phase II, single arm, multicenter trial to determine the efficacy and safety of CTL019 in pediatric patients with relapsed and refractory B-cell acute lymphoblastic leukemia (ELIANA). A phase II, single arm, multicenter trial to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (JULIET). Tisagenlecleucel versus standard of care in adult patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: A randomized, open label, phase III trial (BELINDA). A phase I/II multicenter study evaluating the safety and efficacy of KTE-C19 in subjects with refractory aggressive Non-Hodgkin lymphoma (NHL) (ZUMA-1)
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