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Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies
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Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 27604

Special Issue Editor

Dr. Josee Golay

E-Mail Website
Guest Editor
Hematology Division, Bergamo, Italy
Interests: ​functional analysis of therapeutic antibodies in vitro and in vivo; bispecific antibodies; hematological cancers; somatic cell therapy

Special Issue Information

Dear Colleagues,

Therapeutic monoclonal antibodies were first approved for cancer therapy about 25 years ago. Since then, may antibody-based molecules have been developed and tested in the clinic, and at least 110 molecules have been approved in the US/EU for the therapy of cancer as well as inflammatory, autoimmune, and infectious diseases. To reach this goal, much basic work has been performed in laboratories worldwide, to try to understand how antibody-based drugs work, how to improve their activities, their stability, diminish their toxicity, and facilitate their production. In parallel, many studies have focused on the structure and fine-tuning of natural antibodies, and some of this knowledge has already been applied to improve antibody-based drugs. The aim of this issue is to review recent discoveries that have or are likely to have a significant impact on the successful development of novel or improved therapeutic antibodies in different disease contexts.

We have chosen women scientists for this task. However, we welcome submissions from all authors, irrespective of gender identity.

Dr. Josee Golay
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. Antibodies is an international peer-reviewed open access quarterly 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 1800 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

  • therapeutic antibodies
  • natural antibodies
  • glycosylation
  • antibody variants
  • antibody structure
  • FcRn
  • FcγR
  • isotypes
  • epitope

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Published Papers (5 papers)

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Research

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18 pages, 4071 KiB  
Article
Anticalin N- or C-Terminal on a Monoclonal Antibody Affects Both Production and In Vitro Functionality
by Nicolas Aubrey, Valérie Gouilleux-Gruart, Christine Dhommée, Julie Mariot, Fanny Boursin, Nicolas Albrecht, Cécile Bergua, Cécile Croix, Mäelle Gilotin, Eloi Haudebourg, Catherine Horiot, Laetitia Matthias, Caroline Mouline, Laurie Lajoie, Audrey Munos, Gilles Ferry, Marie-Claude Viaud-Massuard, Gilles Thibault and Florence Velge-Roussel
Antibodies 2022, 11(3), 54; https://doi.org/10.3390/antib11030054 - 22 Aug 2022
Cited by 2 | Viewed by 3071
Abstract
Bispecific antibodies (BsAbs) represent an important advance in innovative therapeutic strategies. Among the countless formats of BsAbs, fusion with molecules such as anticalins linked to a monoclonal antibody (mAb), represents an easy and low-cost way to obtain innovative molecules. We fused an anticalin [...] Read more.
Bispecific antibodies (BsAbs) represent an important advance in innovative therapeutic strategies. Among the countless formats of BsAbs, fusion with molecules such as anticalins linked to a monoclonal antibody (mAb), represents an easy and low-cost way to obtain innovative molecules. We fused an anticalin against human fibronectin to a molecule biosimilar to trastuzumab (H0) or rituximab (R0), in four different positions, two on the N terminal region of heavy or light chains and two on the C terminal region. The eight BsAbs (H family (HF) 1 to 4 and R family (RF) 1 to 4) were produced and their affinity parameters and functional properties evaluated. The presence of anticalin did not change the glycosylation of the BsAb, shape or yield. The antigenic recognition of each BsAb family, Her2 for HF1 to 4 and CD20 for RF1 to 4, was slightly decreased (HF) or absent (RF) for the anticalin N-terminal in the light chain position. The anticalin recognition of FN was slightly decreased for the HF family, but a dramatic decrease was observed for RF members with lowest affinity for RF1. Moreover, functional properties of Abs, such as CD16 activation of NK, CD32-dependent phagocytosis and FcRn transcytosis, confirmed that this anticalin position leads to less efficient BsAbs, more so for RF than HF molecules. Nevertheless, all BsAbs demonstrated affinities for CD16, CD32 and FcRn, which suggests that more than affinity for FcRs is needed for a functioning antibody. Our strategy using anticalin and Abs allows for rapid generation of BsAbs, but as suggested by our results, some positions of anticalins on Abs result in less functionality. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)
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Review

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25 pages, 1041 KiB  
Review
Alternative Routes of Administration for Therapeutic Antibodies—State of the Art
by Aubin Pitiot, Nathalie Heuzé-Vourc’h and Thomas Sécher
Antibodies 2022, 11(3), 56; https://doi.org/10.3390/antib11030056 - 26 Aug 2022
Cited by 21 | Viewed by 8244
Abstract
Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid [...] Read more.
Background: For the past two decades, there has been a huge expansion in the development of therapeutic antibodies, with 6 to 10 novel entities approved each year. Around 70% of these Abs are delivered through IV injection, a mode of administration allowing rapid and systemic delivery of the drug. However, according to the evidence presented in the literature, beyond the reduction of invasiveness, a better efficacy can be achieved with local delivery. Consequently, efforts have been made toward the development of innovative methods of administration, and in the formulation and engineering of novel Abs to improve their therapeutic index. Objective: This review presents an overview of the routes of administration used to deliver Abs, different from the IV route, whether approved or in the clinical evaluation stage. We provide a description of the physical and biological fundamentals for each route of administration, highlighting their relevance with examples of clinically-relevant Abs, and discussing their strengths and limitations. Methods: We reviewed and analyzed the current literature, published as of the 1 April 2022 using MEDLINE and EMBASE databases, as well as the FDA and EMA websites. Ongoing trials were identified using clinicaltrials.gov. Publications and data were identified using a list of general keywords. Conclusions: Apart from the most commonly used IV route, topical delivery of Abs has shown clinical successes, improving drug bioavailability and efficacy while reducing side-effects. However, additional research is necessary to understand the consequences of biological barriers associated with local delivery for Ab partitioning, in order to optimize delivery methods and devices, and to adapt Ab formulation to local delivery. Novel modes of administration for Abs might in fine allow a better support to patients, especially in the context of chronic diseases, as well as a reduction of the treatment cost. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)
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22 pages, 2007 KiB  
Review
Understanding and Modulating Antibody Fine Specificity: Lessons from Combinatorial Biology
by Gertrudis Rojas
Antibodies 2022, 11(3), 48; https://doi.org/10.3390/antib11030048 - 14 Jul 2022
Cited by 4 | Viewed by 7297
Abstract
Combinatorial biology methods such as phage and yeast display, suitable for the generation and screening of huge numbers of protein fragments and mutated variants, have been useful when dissecting the molecular details of the interactions between antibodies and their target antigens (mainly those [...] Read more.
Combinatorial biology methods such as phage and yeast display, suitable for the generation and screening of huge numbers of protein fragments and mutated variants, have been useful when dissecting the molecular details of the interactions between antibodies and their target antigens (mainly those of protein nature). The relevance of these studies goes far beyond the mere description of binding interfaces, as the information obtained has implications for the understanding of the chemistry of antibody–antigen binding reactions and the biological effects of antibodies. Further modification of the interactions through combinatorial methods to manipulate the key properties of antibodies (affinity and fine specificity) can result in the emergence of novel research tools and optimized therapeutics. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)
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16 pages, 4376 KiB  
Review
3D Models as a Tool to Assess the Anti-Tumor Efficacy of Therapeutic Antibodies: Advantages and Limitations
by Virginia Guzzeloni, Lorenzo Veschini, Federica Pedica, Elisabetta Ferrero and Marina Ferrarini
Antibodies 2022, 11(3), 46; https://doi.org/10.3390/antib11030046 - 8 Jul 2022
Cited by 5 | Viewed by 4084
Abstract
Therapeutic monoclonal antibodies (mAbs) are an emerging and very active frontier in clinical oncology, with hundred molecules currently in use or being tested. These treatments have already revolutionized clinical outcomes in both solid and hematological malignancies. However, identifying patients who are most likely [...] Read more.
Therapeutic monoclonal antibodies (mAbs) are an emerging and very active frontier in clinical oncology, with hundred molecules currently in use or being tested. These treatments have already revolutionized clinical outcomes in both solid and hematological malignancies. However, identifying patients who are most likely to benefit from mAbs treatment is currently challenging and limiting the impact of such therapies. To overcome this issue, and to fulfill the expectations of mAbs therapies, it is urgently required to develop proper culture models capable of faithfully reproducing the interactions between tumor and its surrounding native microenvironment (TME). Three-dimensional (3D) models which allow the assessment of the impact of drugs on tumors within its TME in a patient-specific context are promising avenues to progressively fill the gap between conventional 2D cultures and animal models, substantially contributing to the achievement of personalized medicine. This review aims to give a brief overview of the currently available 3D models, together with their specific exploitation for therapeutic mAbs testing, underlying advantages and current limitations to a broader use in preclinical oncology. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)
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16 pages, 1638 KiB  
Review
FcγR-Mediated Trogocytosis 2.0: Revisiting History Gives Rise to a Unifying Hypothesis
by Margaret A. Lindorfer and Ronald P. Taylor
Antibodies 2022, 11(3), 45; https://doi.org/10.3390/antib11030045 - 5 Jul 2022
Cited by 10 | Viewed by 3765
Abstract
There is increasing interest in the clinical implications and immunology of trogocytosis, a process in which the receptors on acceptor cells remove and internalize cognate ligands from donor cells. We have reported that this phenomenon occurs in cancer immunotherapy, in which cells that [...] Read more.
There is increasing interest in the clinical implications and immunology of trogocytosis, a process in which the receptors on acceptor cells remove and internalize cognate ligands from donor cells. We have reported that this phenomenon occurs in cancer immunotherapy, in which cells that express FcγR remove and internalize CD20 and bound mAbs from malignant B cells. This process can be generalized to include other reactions including the immune adherence phenomenon and antibody-induced immunosuppression. We discuss in detail FcγR-mediated trogocytosis and the evidence supporting a proposed predominant role for liver sinusoidal endothelial cells via the action of the inhibitory receptor FcγRIIb2. We describe experiments to test the validity of this hypothesis. The elucidation of the details of FcγR-mediated trogocytosis has the potential to allow for the development of novel therapies that can potentially block or enhance this reaction, depending upon whether the process leads to unfavorable or positive biological effects. Full article
(This article belongs to the Special Issue Women's Special Issue Series: Recent Development for Improved Therapeutic Antibodies)
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