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Cancers
Special Issues
New Horizons to Improve the Efficacy of Tumor-Targeting Therapeutic Antibodies
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New Horizons to Improve the Efficacy of Tumor-Targeting Therapeutic Antibodies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 6223

Special Issue Editors

Dr. Laurent Gros

E-Mail Website1 Website2
Guest Editor
Institut de Recherche en Cancérologie de Montpellier (INSERM U1194-Université de Montpellier-ICM Val d’Aurelle), Campus Val d'Aurelle, 208 rue des apothicaires, 34298 Montpellier cedex 5, France
Interests: antitumor mAbs; microenvironment; immunomodulation; therapeutic combinations; immunity and cancer; new targets
Dr. Thierry Chardès

E-Mail Website1 Website2
Guest Editor
Institut de Recherche en Cancérologie de Montpellier (INSERM U1194-Université de Montpellier-ICM Val d’Aurelle)), Campus Val d'Aurelle, 208 rue des apothicaires, 34298 Montpellier cedex 5, France
Interests: mAbs; antibody; ADC; bispecific; receptor–tyrosine kinases; cathepsins; matricellular proteins; immunity and cancer; pancreas, ovarian and breast cancers

Special Issue Information

Dear Colleagues,

Tumor-targeting monoclonal antibodies (TT-mAbs) are widely used today for the treatment of cancer patients, and their number is constantly increasing. Over the past ten years, numerous studies have shown that the antitumor action of these antibodies greatly exceeds that of simple passive therapies as initially described, with not only the recruitment of immune cells to promote the activation of the early stages of the immune response, but also with the generation of a long-term antitumor protection involving multiple mechanisms. This issue will highlight how the better understanding of the tumor microenvironment associated with the better knowledge in antibody structures and molecular basis of their recognition diversity has recently led to the clinical development of a new generation of TT-mAbs. This issue will focus on the improved efficacy of TT-mAbs by adjusting antibody interactions and drug formats with the tumor milieu, through Fc-engineering to increase immunomodulatory properties, through the identification of new emerging targets and the development of combinatorial approaches, and through the development of new models and delivery devices to study therapeutic antitumor effects.

This Special Issue welcomes reviews, as well as original research articles. Experts on the fields will discuss the role of these improved TT-mAbs in cancer treatment.

Dr. Laurent Gros
Dr. Thierry Chardès
Guest Editors

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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • tumor antigen-targeting Abs and derivatives
  • improved efficacy
  • new targets
  • new formats
  • adjusting Fab/Fc interactions with tumor milieu
  • delivery approaches
  • therapeutic combinations
  • immunomodulation
  • innovative in vitro and mouse models

Published Papers (2 papers)

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Research

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11 pages, 14292 KiB  
Article
A Targeted Catalytic Nanobody (T-CAN) with Asparaginolytic Activity
by Maristella Maggi, Greta Pessino, Isabella Guardamagna, Leonardo Lonati, Cristina Pulimeno and Claudia Scotti
Cancers 2021, 13(22), 5637; https://doi.org/10.3390/cancers13225637 - 11 Nov 2021
Cited by 5 | Viewed by 2171
Abstract
E. coli L-asparaginase is an amidohydrolase (EC 3.5.1.1) which has been successfully used for the treatment of Acute Lymphoblastic Leukemia for over 50 years. Despite its efficacy, its side effects, and especially its intrinsic immunogenicity, hamper its usage in a significant subset of [...] Read more.
E. coli L-asparaginase is an amidohydrolase (EC 3.5.1.1) which has been successfully used for the treatment of Acute Lymphoblastic Leukemia for over 50 years. Despite its efficacy, its side effects, and especially its intrinsic immunogenicity, hamper its usage in a significant subset of cases, thus limiting therapeutic options. Innovative solutions to improve on these drawbacks have been attempted, but none of them have been truly successful so far. In this work, we fully replaced the enzyme scaffold, generating an active, miniaturized form of L-asparaginase by protein engineering of a camel single domain antibody, a class of antibodies known to have a limited immunogenicity in humans. We then targeted it onto tumor cells by an antibody scFv fragment directed onto the CD19 B-cell surface receptor expressed on ALL cells. We named this new type of nanobody-based antibody-drug conjugate “Targeted Catalytic Nanobody” (T-CAN). The new molecule retains the catalytic activity and the binding capability of the original modules and successfully targets CD19 expressing cells in vitro. Thanks to its theoretically reduced immunogenic potential compared to the original molecule, the T-CAN can represent a novel approach to tackle current limitations in L-asparaginase usage. Full article
(This article belongs to the Special Issue New Horizons to Improve the Efficacy of Tumor-Targeting Therapeutic Antibodies)
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Review

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22 pages, 1068 KiB  
Review
Improving Biologics’ Effectiveness in Clinical Oncology: From the Combination of Two Monoclonal Antibodies to Oligoclonal Antibody Mixtures
by Christel Larbouret, Laurent Gros, André Pèlegrin and Thierry Chardès
Cancers 2021, 13(18), 4620; https://doi.org/10.3390/cancers13184620 - 15 Sep 2021
Cited by 9 | Viewed by 3581
Abstract
Monoclonal antibodies have revolutionized the treatment of many diseases, but their clinical efficacy remains limited in some other cases. Pre-clinical and clinical trials have shown that combinations of antibodies that bind to the same target (homo-combinations) or to different targets (hetero-combinations) to mimic [...] Read more.
Monoclonal antibodies have revolutionized the treatment of many diseases, but their clinical efficacy remains limited in some other cases. Pre-clinical and clinical trials have shown that combinations of antibodies that bind to the same target (homo-combinations) or to different targets (hetero-combinations) to mimic the polyclonal humoral immune response improve their therapeutic effects in cancer. The approval of the trastuzumab/pertuzumab combination for breast cancer and then of the ipilimumab/nivolumab combination for melanoma opened the way to novel antibody combinations or oligoclonal antibody mixtures as more effective biologics for cancer management. We found more than 300 phase II/III clinical trials on antibody combinations, with/without chemotherapy, radiotherapy, small molecules or vaccines, in the ClinicalTrials.gov database. Such combinations enhance the biological responses and bypass the resistance mechanisms observed with antibody monotherapy. Usually, such antibody combinations are administered sequentially as separate formulations. Combined formulations have also been developed in which separately produced antibodies are mixed before administration or are produced simultaneously in a single cell line or a single batch of different cell lines as a polyclonal master cell bank. The regulation, toxicity and injection sequence of these oligoclonal antibody mixtures still need to be addressed in order to optimize their delivery and their therapeutic effects. Full article
(This article belongs to the Special Issue New Horizons to Improve the Efficacy of Tumor-Targeting Therapeutic Antibodies)
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