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

Summary

CAR-NK cell therapies have risen to prominence as a unique therapeutic alternative for overcoming challenges associated with CAR-T cell therapies, such as therapy-induced side effects. More than 500 CAR-T and 17 CAR-NK cell trials are currently underway around the world, including four CAR-T cell treatments that are already on the market: Kymriah, Yescarta, Tecartus, and Breyanzi. CAR-immune cell therapies that use precise gene insertion to avoid graft-versus-host disease (GvHD) or a dual targeting method with adapter CARs to avoid therapy resistance caused by antigen loss are being investigated.

Patients characteristics

While most CAR-T cell therapies are designed to target B-cell malignancies, they are also under development for the treatment of different hematologic diseases such as AML. Besides CD33, which was detected on AML blasts in 85–90% of patients and shown to be present on leukemic stem cells (LCSs), also CD123 expression could be detected on AML blasts as well as LCSs in 75–89% of cases.

Introduction

The use of CAR-NK cell therapies has emerged as a potential alternative to CAR-T cell therapies, due to their ability to overcome therapy-induced side effects. With over 500 CAR-T and 17 CAR-NK cell trials currently underway globally, CAR-immune cell therapies that use precise gene insertion or a dual targeting method with adapter CARs are being investigated. CD19-specific CAR-T cells have shown promise in treating B-cell malignancies, while CAR-NK cells offer an intrinsic tumor killing capacity in addition to their CAR-dependent killing mechanism, potentially impeding tumor immune escape mechanisms.

Findings

Regarding CAR-T Cell therapies the following has been found: CD19 positive cancers include diseases with high-priority medical needs such as r/r B-cell acute lymphoblastic leukemia (B-ALL), B-cell chronic lymphocytic leukemia (B-CLL), B-cell Non-Hodgkin lymphoma (B-NHL), and other B-cell malignancies. As CD19 is a B-cell-specific surface protein that is expressed throughout B-cell development, it is present on most B-cell malignancies and therefore a suitable target for CAR-T cell therapies. Therefore, in most clinical cell therapy trials for treatment of B-cell malignancies, CAR-T cells are used which are engineered to express CD19-specific CARs. In addition to that, two studies are being conducted which deploy T cells expressing either CD20-CARs or CD19/CD20-dual-CARs. On the other hand, CAR-NK Cell therapies reveal that NK cells have recently moved into the spotlight as an imposing tool for immunotherapy. While NK cells utilize similar killing mechanisms for eliminating malignant or virally infected cells compared to cytotoxic Tlymphocytes (CTLs), their target recognition mechanism differs substantially. CTLs as part of the adaptive immune response, recognize their targets via a vast variety of clonally rearranged T-cell receptors (TCRs). NK cells on the other hand, as innate lymphoid cells, receive activating and inhibitory signals by their germline-encoded receptor repertoire.Thus, a CAR-NK cell therapy could offer the advantage of an intrinsic tumor killing capacity possessed by CAR-NK cells in addition to their CAR-dependent killing mechanism, impeding tumor immune escape mechanisms.

Conclusion

To date, the first four drugs in the US and three in Europe have been granted marketing authorization, using CAR-modified immune cells as therapies for specific hematological malignancies. As a result, a wide range
of targets must be addressed, including non-malignant targets like HIV-infected cells. As a result, the study provides sufficient reason for CAR-based cellular therapies being extremely promising, and will almost probably lead to the creation of authorized tailored therapeutic options in the future.

Article Reference link: Here Scientific article publishing date: 22/03/2021 Article Identifier:22/03/2021

We believe in Healing Cancer from Within.

Find out more!