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Review
. 2019 Oct;106(4):781-791.
doi: 10.1002/cpt.1396. Epub 2019 Mar 29.

Bispecific Antibodies in the Treatment of Hematologic Malignancies

Johannes Duell  1 , Philip E Lammers  2 , Ivana Djuretic  3 , Allison G Chunyk  4 , Shilpa Alekar  4 , Ira Jacobs  5 , Saar Gill  6
Affiliations
Review

Bispecific Antibodies in the Treatment of Hematologic Malignancies

Johannes Duell et al. Clin Pharmacol Ther. 2019 Oct.

Abstract

Monoclonal antibody therapies are an important approach for the treatment of hematologic malignancies, but typically show low single-agent activity. Bispecific antibodies, however, redirect immune cells to the tumor for subsequent lysis, and preclinical and accruing clinical data support single-agent efficacy of these agents in hematologic malignancies, presaging an exciting era in the development of novel bispecific formats. This review discusses recent developments in this area, highlighting the challenges in delivering effective immunotherapies for patients.

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Conflict of interest statement

J.D. declared no competing interests for this work. P.E.L. is a consultant for Pfizer, Merck, Teva, and Sanofi. I.D. is an employee of Pfizer, has patent applications, and holds stock/stock options in Pfizer. I.J., A.G.C., and S.A. are employees of Pfizer and hold stock/stock options in Pfizer. S.G. has ownership in Carisma Therapeutics and receives research funding from Novartis, Tmunity Therapeutics, and Carisma Therapeutics.

Figures

Figure 1
Figure 1
Comparison of bispecific antibody formats for redirection of cytotoxic effector cells.71 BCMA, B‐cell maturation antigen; BiKEs, bispecific killer cell engagers; BiTE, bispecific T‐cell engager; DART, dual affinity retargeting; Fc, fragment, crystallizable; IgG, immunoglobulin G; NK, natural killer; scFvs, single‐chain variable fragment; TandAb, tandem diabodies; TriKEs, trispecific killer cell engagers; Triomabs, trifunctional, bispecific antibodies. Figures adapted from Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today. 2015;20(7):838–847. Published by Elsevier Ltd. https://doi.org/10.1016/j.drudis.2015.02.008. Licensed under CC BY‐NC‐ND 4.0. ©2015 The authors.
Figure 2
Figure 2
Blinatumomab mode of action. Blinatumomab is a 55‐kDA single‐chain BiTE antibody. It has Fv fragments from anti‐CD3 and anti‐CD19 arms joined by a nonimmunogenic linker, bringing together cytotoxic CD3+T cells and CD19+B cells resulting in granzyme‐mediated and perforin‐mediated B‐cell apoptosis. BiTE, bispecific T‐cell engager.
See this image and copyright information in PMC

References

    1. Spiess, C. , Zhai, Q. & Carter, P.J. Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol. Immunol. 67, 95–106 (2015). - PubMed
    1. Velasquez, M.P. , Bonifant, C.L. & Gottschalk, S. Redirecting T cells to hematological malignancies with bispecific antibodies. Blood 131, 30–38 (2018). - PMC - PubMed
    1. Johnson, S. et al Effector cell recruitment with novel Fv‐based dual‐affinity re‐targeting protein leads to potent tumor cytolysis and in vivo B‐cell depletion. J. Mol. Biol. 399, 436–449 (2010). - PubMed
    1. Moore, P.A. et al Application of dual affinity retargeting molecules to achieve optimal redirected T‐cell killing of B‐cell lymphoma. Blood 117, 4542–4551 (2011). - PubMed
    1. Amgen . Blincyto (blinatumomab) prescribing information <https://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/blincyto...> (2014). Accessed May 2018.

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