Single-Chain Variable Fragment-Based Bispecific Antibodies: Hitting Two Targets with One Sophisticated Arrow.

Authors:
Raoufeh Ahamadi-Fesharaki
Raoufeh Ahamadi-Fesharaki
School of Medicine
Abolfazl Fateh
Abolfazl Fateh
Iranian Institute for Health Sciences Research
Iran
Farzam Vaziri
Farzam Vaziri
Tarbiat Modares University
Iran
Ghasem Solgi
Ghasem Solgi
School of Medicine
Iran
Seyed Davar Siadat
Seyed Davar Siadat
Pasteur Institute of Iran
Tehran | Iran
Fereidoun Mahboudi
Fereidoun Mahboudi
Pasteur Institute of Iran
Iran

Mol Ther Oncolytics 2019 Sep 23;14:38-56. Epub 2019 Mar 23.

Human Antibody Lab, Innovation Center, Pasteur Institute of Iran, Tehran, Iran.

Despite the success of monoclonal antibodies (mAbs) to treat some disorders, the monospecific molecular entity of mAbs as well as the presence of multiple factors and pathways involved in the pathogenesis of disorders, such as various malignancies, infectious diseases, and autoimmune disorders, and resistance to therapy have restricted the therapeutic efficacy of mAbs in clinical use. Bispecific antibodies (bsAbs), by concurrently recognizing two targets, can partly circumvent these problems. Serial killing of tumor cells by bsAb-redirected T cells, simultaneous blocking of two antigens involved in the HIV-1 infection, and concurrent targeting of the activating and inhibitory receptors on B cells to modulate autoimmunity are part of the capabilities of bsAbs. After designing and developing a large number of bsAbs for years, catumaxomab, a full-length bsAb targeting EpCAM and CD3, was approved in 2009 to treat EpCAM-positive carcinomas besides blinatumomab, a bispecific T cell engager antibody targeting CD19 and CD3, which was approved in 2014 to treat relapsed or refractory acute lymphoblastic leukemia. Furthermore, approximately 60 bsAbs are under investigation in clinical trials. The current review aims at portraying different formats of the single-chain variable fragment (scFv)-based bsAbs and shedding light on the scFv-based bsAbs in preclinical development, different phases of clinical trials, and the market.

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Source
http://dx.doi.org/10.1016/j.omto.2019.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463744PMC
September 2019
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