Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany

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.

Immunotherapy for Glioblastoma: Current Progress and Challenges

“…Remarkably, preclinical testing of HER-2-specific NK-92 cells (NK-92/5.28.z) in an orthotopic xenograft mouse model of glioblastoma demonstrated a dramatic increase in survival (200.5 days) compared to mice treated with control NK-92 cells (73 days) (139). Intracranial injection of NK-92/5.28.z cells are being evaluated in the ongoing CAR2BRAIN clinical trial for recurrent glioblastoma, with no toxicities reported thus far at three dose levels (NCT03383978) (140,141). Although the field of CAR-NK cell therapy is still relatively new, preliminary results have been promising, and the first ever clinical trial of CAR-NK cells for glioblastoma will indeed shed light on whether this immunotherapy can bring benefit to patients.…”

Therapeutic cell engineering: designing programmable synthetic genetic circuits in mammalian cells

“…Therapeutic cell engineering killer (NK) cells engineered with CAR (CAR-NK) show fewer adverse effects than T cell therapy, and are more amenable to off-the-shelf manufacturing (Albinger et al, 2021;Schmidt et al, 2021). Although CAR receptors are only functional in immune cells, cell-to-cell contact can also be modulated in other cell types (Fig.…”

Chimeric Antigen Receptor-T Cells: A Pharmaceutical Scope

“…The success of CAR T-cells therapy in cancer is exemplified by numerous clinical trials that have shown that 70–90% complete remission (CR) can be achieved in pediatric and adult patients treated with CD19-directed CAR T-cells ( Xu et al, 2019 ). Based on these growing CAR-T cell immunotherapy achievements, over 500 clinical trials worldwide analyzing CAR-T cells for the treatment of cancer are currently being under evaluation, and the majority are being performed in East Asia (269 trials), followed by the US (225 trials), and Europe (62 ongoing studies) (as registered at clinicaltrials.gov Q3 2020) ( Albinger et al, 2021 ). So far, five CAR-T cell therapy agents were approved by FDA for cancer treatment: Tisagenlecleucel (Kyrmriah®) for treatment of acute lymphoblastic leukemia (ALL) ( Mullard 2017 ), Axicabtagene ciloleucel (Yescarta™) for diffuse large B-cell lymphoma (DLBCL) and also FDA-approval for follicular lymphoma in april 2021 ( Bouchkouj et al, 2019 ), Brexucabtagene autoleucel (Tecartus™) for treatment of mantle cell lymphoma (MCL) ( Al-Juhaishi and Ahmed, 2021 ), Idecabtagene vicleucel (ABECMA®) for treatment of multiple myeloma ( Munshi et al, 2021 ) and Lisocabtagene maraleucel (Breyanzi®) for diffuse large B-cell lymphoma treatment ( Iragavarapu and Hildebrandt 2021 ) ( Table 2 ).…”