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Life
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Bispecific Antibodies: Design, Isolation, Perspectives of Use
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Bispecific Antibodies: Design, Isolation, Perspectives of Use

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 17378

Special Issue Editor

Dr. Sergey Sedyh

E-Mail Website
Guest Editor
SB RAS Institute of Chemical Biology and Fundamental Medicine, Novosibirsk State University, 630090 Novosibirsk, Russia
Interests: catalytic antibodies; bispecific antibodies; human milk; exosomes; horse milk

Special Issue Information

Dear Colleagues,

Bispecific antibodies contain two different antigen-binding sites in one molecule. These ingenious, chemically and genetically engineered constructions have a recent but exciting history; in 2011, these promising molecules were named the “next-generation antibodies”. The generation of a bispecific antibody was first described in 1961; quadromas, expressing two light and heavy chains, were produced in 1983; and in 1984, bispecific antibodies were chemically generated from monoclonal antibodies using bifunctional cross-linkers. In 1985, two HL fragments were united in one bispecific Fab2, and in 1987, it was shown, that bispecific antibodies against T-cell antigen receptors may induce T-cell mediated lysis. The first paper devoted to the use of bispecific antibody in therapy was published in 1992, and therapeutic bispecific antibodies were approved in 2009 in European Union (catumaxomab) and in 2014 in USA (blinatumomab).

This Special Issue of MDPI Life is focused on the new methods of generation and isolation of bispecific antibodies, pharmacokinetics, and perspectives of use in biomedicine and diagnostics.

Dr. Sergey Sedyh
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bispecific antibodies
  • bispecific immunoglobulins
  • cancer immunotherapy
  • trifunctional antibodies
  • Bi-specific T-cell engagers

Published Papers (4 papers)

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Research

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18 pages, 4210 KiB  
Article
The Blood of the HIV-Infected Patients Contains κ-IgG, λ-IgG, and Bispecific κλ-IgG, Which Possess DNase and Amylolytic Activity
by Anna Timofeeva, Sergey Sedykh, Lada Maksimenko, Tatyana Sedykh, Sergey Skudarnov, Tatyana Ostapova, Svetlana Yaschenko, Natalya Gashnikova and Georgy Nevinsky
Life 2022, 12(2), 304; https://doi.org/10.3390/life12020304 - 17 Feb 2022
Cited by 1 | Viewed by 1611
Abstract
Though hundreds of thousands of papers are currently being published on HIV/AIDS, only tens of hundreds of them are devoted to the antibodies generated during the disease. Most of these papers discuss antibodies in HIV/AIDS as a diagnostic tool, and some articles describe [...] Read more.
Though hundreds of thousands of papers are currently being published on HIV/AIDS, only tens of hundreds of them are devoted to the antibodies generated during the disease. Most of these papers discuss antibodies in HIV/AIDS as a diagnostic tool, and some articles describe neutralizing antibodies as a promising treatment. In this paper, we used affinity chromatography and ELISA to isolate natural IgG from the blood of 26 HIV-infected patients. IgG preparations were separated into the subfractions containing different types of light chains, and catalytic activities of subfractions were analyzed. Here, we show for the first time that the blood of HIV patients contains ~20% of bispecific κλ-IgG, presented with all IgG subclasses. Analysis of DNA-hydrolyzing and amylolytic activity show that most IgG preparations and subfractions are catalytically active. Our results expand the possible biological functions of natural IgG in HIV infection. Full article
(This article belongs to the Special Issue Bispecific Antibodies: Design, Isolation, Perspectives of Use)
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15 pages, 35950 KiB  
Article
A Novel Anti-B7-H3 × Anti-CD3 Bispecific Antibody with Potent Antitumor Activity
by Yan Feng, Kun Xie, Yanxin Yin, Bingyu Li, Chenyu Pi, Xiaoqing Xu, Tao Huang, Jingming Zhang, Bo Wang, Hua Gu and Jianmin Fang
Life 2022, 12(2), 157; https://doi.org/10.3390/life12020157 - 21 Jan 2022
Cited by 8 | Viewed by 4282
Abstract
B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The [...] Read more.
B7-H3 plays an important role in tumor apoptosis, proliferation, adhesion, angiogenesis, invasion, migration, and evasion of immune surveillance. It is overexpressed in various human solid tumor tissues. In patients, B7-H3 overexpression correlates with advanced stages, poor clinical outcomes, and resistance to therapy. The roles of B7-H3 in tumor progression make it a potential candidate for targeted therapy. Here, we generated a mouse anti-human B7-H3 antibody and demonstrated its binding activity via Tongji University Suzhou Instituteprotein-based and cell-based assays. We then developed a novel format anti-B7-H3 × anti-CD3 bispecific antibody based on the antibody-binding fragment of the anti-B7-H3 antibody and single-chain variable fragment structure of anti-CD3 antibody (OKT3) and demonstrated that this bispecific antibody mediated potent cytotoxic activities against various B7-H3-positive tumor cell lines in vitro by improving T cell activation and proliferation. This bispecific antibody also demonstrated potent antitumor activity in humanized mice xenograft models. These results revealed that the novel anti-B7-H3 × anti-CD3 bispecific antibody has the potential to be employed in treatment of B7-H3-positive solid tumors. Full article
(This article belongs to the Special Issue Bispecific Antibodies: Design, Isolation, Perspectives of Use)
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14 pages, 3623 KiB  
Article
A Tetravalent Biparatopic Antibody Causes Strong HER2 Internalization and Inhibits Cellular Proliferation
by Filippo Benedetti, Katharina Stadlbauer, Gerhard Stadlmayr, Florian Rüker and Gordana Wozniak-Knopp
Life 2021, 11(11), 1157; https://doi.org/10.3390/life11111157 - 29 Oct 2021
Cited by 3 | Viewed by 3713
Abstract
The overexpression of tyrosine kinase HER2 in numerous cancers, connected with fierce signaling and uncontrolled proliferation, makes it a suitable target for immunotherapy. The acquisition of resistance to currently used compounds and the multiplicity of signaling pathways involved prompted research into the discovery [...] Read more.
The overexpression of tyrosine kinase HER2 in numerous cancers, connected with fierce signaling and uncontrolled proliferation, makes it a suitable target for immunotherapy. The acquisition of resistance to currently used compounds and the multiplicity of signaling pathways involved prompted research into the discovery of novel binders as well as treatment options with multiple targeting and multispecific agents. Here we constructed an anti-HER2 tetravalent and biparatopic symmetrical IgG-like molecule by combining the Fab of pertuzumab with a HER2-specific Fcab (Fc fragment with antigen binding), which recognizes an epitope overlapping with trastuzumab. In the strongly HER2-positive cell line SK-BR-3, the molecule induced a rapid and efficient reduction in surface HER2 levels. A potent anti-proliferative effect, specific for the HER2-positive cell line, was observed in vitro, following the induction of apoptosis, and this could not be achieved with treatment with the mixture of pertuzumab and the parental Fcab. The inhibitory cytotoxic effect of our antibody as a single agent makes it a promising contribution to the armory of anti-cancer molecules directed against HER2-addicted cells. Full article
(This article belongs to the Special Issue Bispecific Antibodies: Design, Isolation, Perspectives of Use)
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Review

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17 pages, 411 KiB  
Review
BiTEs, DARTS, BiKEs and TriKEs—Are Antibody Based Therapies Changing the Future Treatment of AML?
by Cecily Allen, Amer M. Zeidan and Jan Philipp Bewersdorf
Life 2021, 11(6), 465; https://doi.org/10.3390/life11060465 - 23 May 2021
Cited by 25 | Viewed by 6985
Abstract
Nearly four decades after their conceptualization, antibody-based therapies are slowly being added to the treatment landscape of acute myeloid leukemia (AML). While the antibody–drug conjugate gemtuzumab ozogamicin is the only antibody-based therapy that has been approved for AML treatment thus far, several bispecific [...] Read more.
Nearly four decades after their conceptualization, antibody-based therapies are slowly being added to the treatment landscape of acute myeloid leukemia (AML). While the antibody–drug conjugate gemtuzumab ozogamicin is the only antibody-based therapy that has been approved for AML treatment thus far, several bispecific antibodies have been developed and shown early encouraging results. Bispecific antibodies comprise a wide variety of constructs that share the common concept of simultaneous binding of a surface target on malignant cells and most commonly CD3 on T cells leading to an endogenous, HLA-independent, immune response against malignant cells. However, the use of bispecific antibodies in AML has been limited by the absence of highly specific leukemia-associated antigens leading to on-target, off-leukemia side effects as well as reduced efficacy due to antigen escape. Herein, we discuss the history and evolution of bispecific T cell engagers as well as various adaptations such as dual affinity retargeting antibodies, bi- and tri-specific killer engager antibodies. Common side effects including cytokine release syndrome and management thereof are highlighted. Lastly, we expound on the future direction and integration of such antibody-based therapies with other immunotherapies (programmed cell death-1 inhibitors and chimeric antigen receptor T cells). Full article
(This article belongs to the Special Issue Bispecific Antibodies: Design, Isolation, Perspectives of Use)
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