Update on the current and future use of CAR‐T to treat multiple myeloma

Abstract

Chimeric antigen receptor T‐cell (CAR‐T) therapy has become an important intervention in the management of relapsed and relapsed/refractory multiple myeloma (MM). Currently, B‐cell maturation antigen (BCMA) is the most targeted surface protein due to its ubiquitous expression on plasma cells, with increasing expression of this essential transmembrane protein on malignant plasma cells as patients develop more advanced disease. This review will explore the earliest CAR‐T trials in myeloma, discuss important issues involved in CAR‐T manufacturing and processing, as well as review current clinical trials that led to the approval of the two commercially available CAR‐T products, Idecabtagene vicleucel and ciltacabtagene autoleucel. The most recent data from trials investigating the use of CAR‐T as an earlier line of therapy will be presented. Finally, the problem of relapses after CAR‐T will be presented, including several theories as to why CAR‐T therapies fail and possible clinical caveats. The next generation of MM‐specific CAR‐T will likely include new targets such as G‐protein‐coupled receptor class C, Group 5, member D (GPRC5D) and signaling lymphocyte activation molecular Family 7 (SLAMF7). The role of CAR‐T in the treatment of MM will undoubtedly increase exponentially in the next decade.

New facet of CARs: HBV-specific CARs as inhibitors of virus morphogenesis and release

“…Eberhard Hildt , 1,2 Jianming Hu 3 Although safe and effective vaccines against HBV (hepatitis B virus) are available, there are worldwide more than 2 billion people who had an HBV infection and about 250 million people suffering from chronic HBV infection. Chronic HBV infection is a major cause for liver diseases such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC).…”

“…This approach has shown promising results for the therapy of leukaemias (B-cell acute lymphatic leukaemia), non-Hodgkin's lymphoma and chronic lymphatic leukaemia) and some CAR-T cell products have gained market authorisation in the EU and USA. 3 CAR-T cellbased therapies for chronic HBV are still in the early phase of development but are considered as a novel and promising therapeutic approach.…”

Toll-like receptor signaling in multiple myeloma cells promotes the expression of pro-survival genes B-cell lymphoma 2 and MYC and modulates the expression of B-cell maturation antigen

“…First-line treatment often includes a combination of drugs of different classes, including proteasome inhibitors (PIs), immunomodulating drugs, monoclonal antibodies targeting CD38, and corticosteroids (1). A monoclonal antibody-drug conjugate targeting B-cell maturation antigen (BCMA) expressed on the surface of MM cells and chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has been approved to treat patients who are refractory to previous treatment strategies (7). Bispecific T-cell engagers (BiTEs) targeting BCMA and CD3 have also shown great promise (8)(9)(10).…”

DataSheet_1.pdf

“…First-line treatment often includes a combination of drugs of different classes, including proteasome inhibitors (PIs), immunomodulating drugs, monoclonal antibodies targeting CD38, and corticosteroids (1). A monoclonal antibody-drug conjugate targeting B-cell maturation antigen (BCMA) expressed on the surface of MM cells and chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has been approved to treat patients who are refractory to previous treatment strategies (7). Bispecific T-cell engagers (BiTEs) targeting BCMA and CD3 have also shown great promise (8)(9)(10).…”