Bispecific Antibodies for Lymphoid Malignancy Treatment

Abstract

Backgroud: The introduction of highly active immunotherapies has changed the outcome of B-cell non-Hodgkin lymphomas (B-NHLs) in the last two decades. Since then, important progress has been shown using newer and more active immunotherapies, including chimeric antigen receptor T-cell therapy (CAR-T), conjugated monoclonal antibodies, and bispecific antobodies, which currently plays a significant role in the treatment of diffuse large B-cell (DLBCL), follicular (FL), and mantle cell (MCL) lymphoma.

Purpose: In this review, we provide an updated overview of recently completed and ongoing BsAb trials in patients with relapsed/refractory(R/R) B-NHL and Hodgkin's lymphoma, including single-agent results, emerging combinations, safety data, and novel constructs.

Conclusions: Bispecific antibodies (BsAbs) are a novel class of "off-the-shelf" T-cell-redirecting drugs capable of targeting various cell-surface antigens. New antigen targets are currently under investigation, such as CD19 × CD3 and CD30 × CD3 or CD30 × CD16, in different settings. BsAbs are among the most promising therapeutic options for lymphoma today since they have demonstrated significant single-agent activity, along with a manageable toxicity profile, in patients with heavily pretreated B-NHL.

Keywords: B-cell lymphoma (B-NHL); CD19; CD20; CD30; antibody; bispecific T-cell engagers (BiTEs); bispecific antibodies (BsAbs).

Figure 1

Simplified molecular structure of anti-CD20, anti-CD19, and anti-CD30 bispecific products. Abbreviations: BiTE (bispecific T-cell engager), ScFV (single-chain variable fragment), and TandAbs (tandem diabodies).

Figure 2

Mechanisms of action and targets of anti-CD20, anti-CD19, and anti-CD30 bispecific products. Abbreviations: BiTE (Bispecific T-cell Engager), HRS cell (Hodgkin and Reed Sternberg cell), NHL cell (Non-Hodgkin Lymphoma cell), and TandAbs (Tandem diabodies).