Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jun 11;14(6):1243.
doi: 10.3390/pharmaceutics14061243.

Bispecific Antibodies in Cancer Immunotherapy: A Novel Response to an Old Question

Camila Ordóñez-Reyes  1   2 , Juan Esteban Garcia-Robledo  1   3 , Diego F Chamorro  1   2 , Andrés Mosquera  1 , Liliana Sussmann  4 , Alejandro Ruiz-Patiño  1   2 , Oscar Arrieta  5 , Lucia Zatarain-Barrón  5 , Leonardo Rojas  1 , Alessandro Russo  6 , Diego de Miguel-Perez  7 , Christian Rolfo  7 , Andrés F Cardona  1   2   8
Affiliations
Review

Bispecific Antibodies in Cancer Immunotherapy: A Novel Response to an Old Question

Camila Ordóñez-Reyes et al. Pharmaceutics. .

Abstract

Immunotherapy has redefined the treatment of cancer patients and it is constantly generating new advances and approaches. Among the multiple options of immunotherapy, bispecific antibodies (bsAbs) represent a novel thoughtful approach. These drugs integrate the action of the immune system in a strategy to redirect the activation of innate and adaptive immunity toward specific antigens and specific tumor locations. Here we discussed some basic aspects of the design and function of bsAbs, their main challenges and the state-of-the-art of these molecules in the treatment of hematological and solid malignancies and future perspectives.

Keywords: bispecific antibodies; cancer therapy; immune restoration; immunotherapy.

PubMed Disclaimer

Conflict of interest statement

Andrés F. Cardona discloses financial research support from Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb and The Foundation for Clinical and Applied Cancer Research—FICMAC. Additionally, he was linked with and received honoraria as advisor, participate in speakers’ bureau and gave expert testimony to Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Pfizer, Novartis, Celldex Therapeutics, Foundation Medicine, Eli Lilly and Foundation for Clinical and Applied Cancer Research—FICMAC. Oscar Arrieta reports personal fees from Pfizer, grants and personal fees from Astra zeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Lilly, personal fees from Merck, personal fees from Bristol Myers Squibb, grants and personal fees from Roche, outside the submitted work. Christian Rolfo is a current employee of the Center for Thoracic Oncology at Tisch Cancer Institute, Mount Sinai Health System and Icahn School of Medicine. He reports receiving supported research funding from Lung Cancer Research Foundation-Pfizer; receiving non-financial research support from Guardant Health; providing advisory services to ARCHER, Inivata, EMD Serono, BMS, Novartis, Boston Pharmaceuticals, Pfizer, Mirati, and Eisai; providing speaker services to MSD, AstraZeneca, Roche, and Guardant Health; and participating in the Safety Monitoring Board for EMD Serono.

Figures

Figure 1
Figure 1
A depiction of some current multivalent antibody structures under study. (A) Trifuctional antibodies conserved their Fc domain to be able to bind to cells expressing Fc receptors. (B) BiTEs (bispecific T-cell engagers). (C) BiKEs (bispecific NK-cell engagers). (D) TriKEs (trispecific NK-cell engagers). (E) Single-domain antibodies only have one variable chain per target, they are usually made from heavy chain nanobodies derived from the structure of heavy-chain only camelid antibodies. (F) HLE BiTEs (half-life extended bispecific T-cell engagers) are BiTEs with an Fc portion that increases its half-life. (G) DARTs (dual affinity retargeting antibodies). Created with BioRender.com.
Figure 2
Figure 2
Description of the mechanism of NK-Bias; these antibodies target a tumor-related antigen and bind membrane receptors on NK cells allowing a spatial and molecular immune-mediated cell-killing process. We also show some of the tumor-associated targets that currently have been studied for therapy. Epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor 2 (HER2), prostate specific membrane antigen (PSMA), B-cell maturation antigen (BCMA), CD19, CD20, CD123, CD33, CD30 (cluster of differentiation [CD]).
See this image and copyright information in PMC

References

    1. Nuñez-Prado N., Compte M., Harwood S., Álvarez-Méndez A., Lykkemark S., Sanz L., Álvarez-Vallina L. The Coming of Age of Engineered Multivalent Antibodies. Drug Discov. Today. 2015;20:588–594. doi: 10.1016/j.drudis.2015.02.013. - DOI - PubMed
    1. Labrijn A., Janmaat M., Reichert J., Parren P. Bispecific Antibodies: A Mechanistic Review of the Pipeline. Nat. Rev. Drug Discov. 2019;18:585–608. doi: 10.1038/s41573-019-0028-1. - DOI - PubMed
    1. Viardot A., Bargou R. Bispecific Antibodies in Haematological Malignancies. Cancer Treat. Rev. 2018;65:87–95. doi: 10.1016/j.ctrv.2018.04.002. - DOI - PubMed
    1. Waldman A.D., Fritz J.M., Lenardo M.J. A Guide to Cancer Immunotherapy: From T Cell Basic Science to Clinical Practice. Nat. Rev. Immunol. 2020;20:651–668. doi: 10.1038/s41577-020-0306-5. - DOI - PMC - PubMed
    1. Trabolsi A., Arumov A., Schatz J.H., Alerts E. T Cell—Activating Bispecific Antibodies in Cancer Therapy. J. Immunol. 2022;203:585–592. doi: 10.4049/jimmunol.1900496. - DOI - PubMed

LinkOut - more resources