NEJM: GPRC5D-targeted CAR-T cell therapy for multiple myeloma treatment

Multiple myeloma (MM) is a hematologic malignancy that destroys bones, immune systems, kidneys, and red blood cell counts, usually leading to extensive bone destruction, accompanied by lytic bone lesions, osteopenia, and pathological fractures, and is common in older patients

At present, the targeted treatment methods of MM in clinical practice mainly include immunomodulatory drugs (thalidomide, lenalidomide, pomadomide), proteasome inhibitors (bortezomib, carfezomib, isazomib) and anti-CD38 monoclonal antibodies

GPRC5D is a G protein-coupled receptor C5 family subtype D, which belongs to an orphan receptor and is a 7-time transmembrane protein

MM cell surface specific target

In addition, GPRC5D is expressed independently of BCMA, so it can be developed as a single or dual target, providing a new treatment path for multiple myeloma patients, and the clinical value is highlighted

B-cell mature antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has responded in patients with advanced myeloma, but relapse is common

In

Results

ConclusionThe

Comments:

GPRC5D has become the next competitive target for

In addition, Johnson & Johnson's Talquetamab (JNJ-64407564), a first-in-class bispecific antibody that targets both CD3 and GPRC5D, launched a Phase II clinical trial

At the 2020 ASH Annual Meeting, Johnson & Johnson released preliminary data

At the 2022 ASCO Annual Meeting, Yuanqi Biologics, a Chinese biotech company, published in the form of an oral report the Phase I POLARIS clinical trial data conducted by researchers of OriCAR-017 (autologous GPRC5D-targeted chimeric antigen receptor T cells) for the

This single intravenous infusion of OriCAR-017 showed early, in-depth and long-lasting clinical efficacy in all dose groups for relapsed refractory multiple myeloma, including cases

Clinical benefit was observed in all dose groups of the study, with objective response rate (ORR) of 100% and strict sense complete response/complete response rate (sCR/CR) of 60%, of which 5 cases of BCMA-CART treatment relapse achieved 2 cases of complete remission in the strict sense, 2 cases of very good partial remission and 1 case of partial remission

In addition, the GPRC5D CAR-T jointly developed by Uruco and MSKCC is currently in clinical phase I and has not yet disclosed clinical data

Original Source:

GPRC5D-Targeted CAR T Cells for Myeloma