JNJ-89853413: A First-in-Class CD33xVδ2 Bispecific T-cell Engager for Hematological Malignancies - Preclinical Profile and Phase 1 Clinical Development

1. Introduction to JNJ-89853413: A Novel Bispecific Antibody

1.1. Overview and Nomenclature

JNJ-89853413, also identified by the developmental code CD33xVδ2, is an investigational biopharmaceutical agent engineered as a bispecific antibody.[1] This molecule is designed to function as an immunotherapy, specifically by engaging a distinct subset of T-lymphocytes, known as Vδ2 T-cells, to recognize and eliminate malignant cells that express the CD33 surface antigen.[1] Its development signifies an innovative approach within the field of oncology, aiming to harness specific components of the immune system for targeted cancer therapy. The "first-in-class" designation underscores its unique mechanism and target combination within the current therapeutic landscape.[3]

1.2. Drug Class

JNJ-89853413 is categorized as a bispecific T-cell engager (BiTE).[4] More precisely, it is a Vδ2 T-cell engaging antibody, differentiating it from conventional T-cell engagers that typically target the CD3 protein on pan-T-cells.[3] This classification highlights its specific interaction with Vδ2 T-cells, which are a component of the gamma-delta (γδ) T-cell population.

1.3. Developers and Collaboration

The development of JNJ-89853413 is spearheaded by Janssen Research & Development, LLC, a pharmaceutical company of Johnson & Johnson.[5] A critical component of the antibody, the anti-Vδ2 VHH (Variable Heavy chain of Heavy chain antibodies) arm, was generated by LAVA Therapeutics N.V..[3] Subsequent to this, Janssen undertook the humanization of the molecule and performed post-translation modification (PTM) risk mitigation to optimize its characteristics for clinical use.[3]