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Review
. 2024 Oct 10:15:1424925.
doi: 10.3389/fimmu.2024.1424925. eCollection 2024.

Bispecific antibody targets and therapies in multiple myeloma

Matthew Rees #  1   2 , Nadine Abdallah #  1 , Binoy Yohannan #  1   3 , Wilson I Gonsalves  1
Affiliations
Review

Bispecific antibody targets and therapies in multiple myeloma

Matthew Rees et al. Front Immunol. .

Abstract

Recently, several bispecific antibodies (BsAbs) have been approved for the treatment of relapsed multiple myeloma (MM) after early phase trials in heavily pre-treated patients demonstrated high response rates and impressive progression-free survival with monotherapy. These BsAbs provide crucial treatment options for relapsed patients and challenging decisions for clinicians. Evidence on the optimal patient population, treatment sequence, and duration of these therapeutics is unknown and subject to active investigation. While rates of cytokine release syndrome and neurotoxicity appear to be lower with BsAbs than with CAR T-cells, morbidity from infection is high and novel pathways of treatment resistance arise from the longitudinal selection pressure of chronic BsAb therapy. Lastly, a wealth of novel T-cell engagers with unique antibody-structures and antigenic targets are under active investigation with promising early outcome data. In this review, we examine the mechanism of action, therapeutic targets, combinational approaches, sequencing and mechanisms of disease relapse for BsAbs in MM.

Keywords: T-cell engagers; bispecific antibodies; combination (combined) therapy; immunotherapy; multiple myeloma; sequencing; treatment resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Bispecific antibody structure and function: (A) The main formats of bispecific antibodies (BsAbs) in multiple myeloma are the 1) bispecific T-cell engagers (BiTEs) (right) and 2) IgG-like BsAbs (left), which are composed of one (1 + 1) or two (1 + 2) binding sites for the target antigen: (B) BsAbs bind simultaneously to the CD3 receptor on T-cells and the target antigen on the plasma cell surface, bringing them close. This leads to T-cell activation and expansion and the release of perforin and granzymes, leading to plasma cell death.
Figure 2
Figure 2
Targets for bispecific antibodies in multiple myeloma: BCMA, B-cell maturation antigen; CD, cluster of differentiation; Fc, fragment crystallizable; FcRL5, Fc receptor-like 5; GPRC5D, G protein-coupled receptor class C group 5 member D; NK, natural killer; NY-ESO-1, New York esophageal squamous cell carcinoma 1; SLAMF7, lymphocyte activation molecule family member 7. *FDA approved.
Figure 3
Figure 3
Resistance to bispecific antibody therapies.
See this image and copyright information in PMC

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