A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma.

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Pillarisetti K, Edavettal S, Mendonca M, Li Y, Tornetta M, Babich A, Majewski N, Husovsky M, Reeves D, Walsh E, Chin D, Luistro L, Joseph J, Chu G, Packman K, Shetty S, Elsayed Y, Attar R, Gaudet F

A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma.

Blood. 2020 Apr 9;135(15):1232-1243. doi: 10.1182/blood.2019003342.

PubMed ID

32040549 [ View in PubMed

]

Abstract

T-cell-mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein-coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells. Here, we demonstrate that GPRC5D protein is present on the surface of MM cells and describe JNJ-64407564, a GPRC5DxCD3 bispecific antibody that recruits CD3+ T cells to GPRC5D+ MM cells and induces killing of GPRC5D+ cells. In vitro, JNJ-64407564 induced specific cytotoxicity of GPRC5D+ cells with concomitant T-cell activation and also killed plasma cells in MM patient samples ex vivo. JNJ-64407564 can recruit T cells and induce tumor regression in GPRC5D+ MM murine models, which coincide with T-cell infiltration at the tumor site. This antibody is also able to induce cytotoxicity of patient primary MM cells from bone marrow, which is the natural site of this disease. GPRC5D is a promising surface antigen for MM immunotherapy, and JNJ-64407564 is currently being evaluated in a phase 1 clinical trial in patients with relapsed or refractory MM (NCT03399799).

DrugBank Data that Cites this Article

Drugs

Talquetamab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Talquetamab	G-protein coupled receptor family C group 5 member D	Protein	Humans	Yes	Antibody	Details
Talquetamab	T-cell surface glycoprotein CD3 (Protein Group)	Protein group	Humans	Yes	Antibody	Details