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Antibodies
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Antibody Drug and Target Discovery for Cancer Therapies
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Antibody Drug and Target Discovery for Cancer Therapies

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

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 16592

Special Issue Editor

Dr. Nicolas Bery

E-Mail Website
Guest Editor
Centre de Recherches en Cancérologie de Toulouse (CRCT), U1037 INSERM, Université Toulouse III, U5071 CNRS, 31100 Toulouse, France
Interests: single domain antibodies; antibody mimetics; intracellular antibodies; intracellular antibody-based degraders; protein-protein interaction inhibition; phage display; cell-based screening; cancer therapeutic targets; pancreatic cancer

Special Issue Information

Dear Colleagues,

Antibodies are a class of biological therapeutics that is quickly expanding with now more than 100 antibodies approved by the FDA. All of these drugs bind extracellular or transmembrane targets and most of them inhibit their target function by blocking receptor-ligand interactions. However, therapeutic antibodies are not limited to canonical antibodies and other avenues such as antibody-drug conjugate (ADC) or bispecific antibodies in oncoimmunology are exciting possibilities for cancer therapies. In the future, intracellular antibodies—i.e., expressed within the cells—may have a huge impact on cancer treatments once their delivery will be efficient for inhibiting intracellular targets in clinic.     

This Special Issue of Antibodies aims to provide an up-to-date overview of therapeutic antibodies but also of the use of antibodies (or fragment antibodies) for discovering novel therapeutic targets of interest (either extra or intracellular ones) or novel inhibitory mechanisms and their validation. In this Special Issue, original research articles and reviews are welcome and should cover the aforementioned topics applied to cancer therapies.

Dr. Nicolas Bery
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 targets
  • intra or extracellular targets
  • antibody drug conjugates
  • cancer immunotherapy
  • bispecific T-cell engager antibodies
  • intracellular antibodies
  • target validation
  • novel inhibitory mechanisms

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Published Papers (3 papers)

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Review

13 pages, 2577 KiB  
Review
Intracellular Antibodies for Drug Discovery and as Drugs of the Future
by T. H. Rabbitts
Antibodies 2023, 12(1), 24; https://doi.org/10.3390/antib12010024 - 16 Mar 2023
Cited by 7 | Viewed by 4690
Abstract
The application of antibodies in cells was first shown in the early 1990s, and subsequently, the field of intracellular antibodies has expanded to encompass antibody fragments and their use in target validation and as engineered molecules that can be fused to moieties (referred [...] Read more.
The application of antibodies in cells was first shown in the early 1990s, and subsequently, the field of intracellular antibodies has expanded to encompass antibody fragments and their use in target validation and as engineered molecules that can be fused to moieties (referred to as warheads) to replace the Fc effector region of a whole immunoglobulin to elicit intracellular responses, such as cell death pathways or protein degradation. These various forms of intracellular antibodies have largely been used as research tools to investigate function within cells by perturbing protein activity. New applications of such molecules are on the horizon, namely their use as drugs per se and as templates for small-molecule drug discovery. The former is a potential new pharmacology that could harness the power and flexibility of molecular biology to generate new classes of drugs (herein referred to as macrodrugs when used in the context of disease control). Delivery of engineered intracellular antibodies, and other antigen-binding macromolecules formats, into cells to produce a therapeutic effect could be applied to any therapeutic area where regulation, degradation or other kinds of manipulation of target proteins can produce a therapeutic effect. Further, employing single-domain antibody fragments as competitors in small-molecule screening has been shown to enable identification of drug hits from diverse chemical libraries. Compounds selected in this way can mimic the effects of the intracellular antibodies that have been used for target validation. The capability of intracellular antibodies to discriminate between closely related proteins lends a new dimension to drug screening and drug development. Full article
(This article belongs to the Special Issue Antibody Drug and Target Discovery for Cancer Therapies)
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20 pages, 11965 KiB  
Review
Therapeutic Potential of Intrabodies for Cancer Immunotherapy: Current Status and Future Directions
by Thomas Böldicke
Antibodies 2022, 11(3), 49; https://doi.org/10.3390/antib11030049 - 18 Jul 2022
Cited by 11 | Viewed by 5435
Abstract
Tumor cells are characterized by overexpressed tumor-associated antigens or mutated neoantigens, which are expressed on the cell surface or intracellularly. One strategy of cancer immunotherapy is to target cell-surface-expressed tumor-associated antigens (TAAs) with therapeutic antibodies. For targeting TAAs or neoantigens, adoptive T-cell therapies [...] Read more.
Tumor cells are characterized by overexpressed tumor-associated antigens or mutated neoantigens, which are expressed on the cell surface or intracellularly. One strategy of cancer immunotherapy is to target cell-surface-expressed tumor-associated antigens (TAAs) with therapeutic antibodies. For targeting TAAs or neoantigens, adoptive T-cell therapies with activated autologous T cells from cancer patients transduced with novel recombinant TCRs or chimeric antigen receptors have been successfully applied. Many TAAs and most neoantigens are expressed in the cytoplasm or nucleus of tumor cells. As alternative to adoptive T-cell therapy, the mRNA of intracellular tumor antigens can be depleted by RNAi, the corresponding genes or proteins deleted by CRISPR-Cas or inactivated by kinase inhibitors or by intrabodies, respectively. Intrabodies are suitable to knockdown TAAs and neoantigens without off-target effects. RNA sequencing and proteome analysis of single tumor cells combined with computational methods is bringing forward the identification of new neoantigens for the selection of anti-cancer intrabodies, which can be easily performed using phage display antibody repertoires. For specifically delivering intrabodies into tumor cells, the usage of new capsid-modified adeno-associated viruses and lipid nanoparticles coupled with specific ligands to cell surface receptors can be used and might bring cancer intrabodies into the clinic. Full article
(This article belongs to the Special Issue Antibody Drug and Target Discovery for Cancer Therapies)
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21 pages, 1407 KiB  
Review
Antibody-Based Approaches to Target Pancreatic Tumours
by Marie Sorbara, Pierre Cordelier and Nicolas Bery
Antibodies 2022, 11(3), 47; https://doi.org/10.3390/antib11030047 - 12 Jul 2022
Cited by 8 | Viewed by 5380
Abstract
Pancreatic cancer is an aggressive cancer with a dismal prognosis. This is due to the difficulty to detect the disease at an early and curable stage. In addition, only limited treatment options are available, and they are confronted by mechanisms of resistance. Monoclonal [...] Read more.
Pancreatic cancer is an aggressive cancer with a dismal prognosis. This is due to the difficulty to detect the disease at an early and curable stage. In addition, only limited treatment options are available, and they are confronted by mechanisms of resistance. Monoclonal antibody (mAb) molecules are highly specific biologics that can be directly used as a blocking agent or modified to deliver a drug payload depending on the desired outcome. They are widely used to target extracellular proteins, but they can also be employed to inhibit intracellular proteins, such as oncoproteins. While mAbs are a class of therapeutics that have been successfully employed to treat many cancers, they have shown only limited efficacy in pancreatic cancer as a monotherapy so far. In this review, we will discuss the challenges, opportunities and hopes to use mAbs for pancreatic cancer treatment, diagnostics and imagery. Full article
(This article belongs to the Special Issue Antibody Drug and Target Discovery for Cancer Therapies)
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