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Cancers
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Antibody-Drug Conjugates for the Treatment of Cancer
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Antibody-Drug Conjugates for the Treatment of Cancer

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

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 19750

Special Issue Editor

Prof. Gianluca Sala

E-Mail Website
Guest Editor
Department of Medical, Oral and Biotechnological Sciences, University G D’Annunzio Chieti-Pescara, Via Dei Polacchi, 11, 66100, Chieti, Italy
Interests: cancer biology; cancer therapy; biomarker; development of targeted therapeutics in oncology

Special Issue Information

Dear Colleagues,

Antibody–drug conjugates (ADCs) are pharmaceutical compounds created to meet the need to combine high tumor-killing activity with the lowest off-target toxicity. They represent one of the most successful examples of targeted therapy in oncology. Indeed, cancer treatment has seen significant advances and growth in terms of therapy options, thanks to a significant increase in carriers available for selective drug delivery.

ADCs have complex molecular structures, including a highly selective monoclonal antibody (mAb) directed against a tumor antigen, potent cytotoxic small molecule (payload), and linker connecting these two moieties. The chemistry used to link the toxin to the antibody backbone and DAR (drug–antibody ratio) may play a critical role in the activity of an ADC, both influencing cell killing activity and off-target toxicity as well as pharmacokinetic properties. Two main categories of highly potent cytotoxic anticancer agents are used in antibody–drug conjugates: microtubule-disrupting agents and DNA-modifying agents. The choice of the payload used to arm the antibody is a prime step in the development of an ADC as the sensitivity to cytotoxic agents varies between tumors of different origin. Finally, ADCs can be directed against both tumor and stromal components, constructed using internalizing or non-internalizing antibodies, and different mechanisms of action can be designed to increase the therapeutic activity of an ADC according to the used target.

In summary, the development of a perfect ADC requires the optimization of multiple parameters, including antigens, antibodies, linkers, payloads, and the payload–linker connection.

ADC development and clinical use is a fast, evolving area. Nowadays, nine ADCs have received market approval for oncotherapies, and around 90 new candidates are currently under consideration in clinical trials as both single agents and in combination regimens. Overall, the promising results obtained from preclinical and clinical studies are greatly encouraging the discovery of novel compounds to increase available effective therapies for cancer patients.

This Special Issue of Cancers will focus on new research articles and updated reviews on all aspects related to preclinical and clinical advances in the development of novel ADCs for the treatment of cancer.

Prof. Gianluca Sala
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 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

  • antibody–drug conjugate
  • monoclonal antibody
  • payload
  • targeted therapy
  • combination therapy
  • biomarkers

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Published Papers (3 papers)

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Review

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18 pages, 17414 KiB  
Review
Generation of Antibody-Drug Conjugate Resistant Models
by Lucía Gandullo-Sánchez, Alberto Ocaña and Atanasio Pandiella
Cancers 2021, 13(18), 4631; https://doi.org/10.3390/cancers13184631 - 15 Sep 2021
Cited by 8 | Viewed by 4160
Abstract
In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of [...] Read more.
In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of clinical development. Despite the efficacy of this type of drug, the tumors of some patients may result in resistance to ADCs. Due to this, it is essential not only to comprehend resistance mechanisms but also to develop strategies to overcome resistance to ADCs. To reach these goals, the generation and use of preclinical models to study those mechanisms of resistance are critical. Some cells or patient tumors may result in primary resistance to the action of an ADC, even if they express the antigen against which the ADC is directed. Isolated primary tumoral cells, cell lines, or patient explants (patient-derived xenografts) with these characteristics can be used to study primary resistance. The most common method to generate models of secondary resistance is to treat cancer cell lines or tumors with an ADC. Two strategies, either continuous treatment with the ADC or intermittent treatment, have successfully been used to develop those resistance models. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates for the Treatment of Cancer)
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23 pages, 3586 KiB  
Review
Antibody–Drug Conjugates for the Treatment of Breast Cancer
by Chiara Corti, Federica Giugliano, Eleonora Nicolò, Liliana Ascione and Giuseppe Curigliano
Cancers 2021, 13(12), 2898; https://doi.org/10.3390/cancers13122898 - 9 Jun 2021
Cited by 45 | Viewed by 10134
Abstract
Metastatic breast cancer (BC) is currently an incurable disease. Besides endocrine therapy and targeted agents, chemotherapy is often used in the treatment of this disease. However, lack of tumor specificity and toxicity associated with dose exposure limit the manageability of cytotoxic agents. Antibody–drug [...] Read more.
Metastatic breast cancer (BC) is currently an incurable disease. Besides endocrine therapy and targeted agents, chemotherapy is often used in the treatment of this disease. However, lack of tumor specificity and toxicity associated with dose exposure limit the manageability of cytotoxic agents. Antibody–drug conjugates (ADCs) are a relatively new class of anticancer drugs. By merging the selectivity of monoclonal antibodies with the cytotoxic properties of chemotherapy, they improve the therapeutic index of antineoplastic agents. Three core components characterize ADCs: the antibody, directed to a target antigen; the payload, typically a cytotoxic agent; a linker, connecting the antibody to the payload. The most studied target antigen is HER2 with some agents, such as trastuzumab deruxtecan, showing activity not only in HER2-positive, but also in HER2-low BC patients, possibly due to a bystander effect. This property to provide a cytotoxic impact also against off-target cancer cells may overcome the intratumoral heterogeneity of some target antigens. Other cancer-associated antigens represent a strategy for the development of ADCs against triple-negative BC, as shown by the recent approval of sacituzumab govitecan. In this review, we discuss the current landscape of ADC development for the treatment of BC, as well as the possible limitations of this treatment. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates for the Treatment of Cancer)
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Other

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28 pages, 1188 KiB  
Systematic Review
Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review
by Vittoria Perrotti, Vito Carlo Alberto Caponio, Marco Mascitti, Lorenzo Lo Muzio, Adriano Piattelli, Corrado Rubini, Emily Capone and Gianluca Sala
Cancers 2021, 13(13), 3126; https://doi.org/10.3390/cancers13133126 - 22 Jun 2021
Cited by 16 | Viewed by 3911
Abstract
Background: Antibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed [...] Read more.
Background: Antibody-drug conjugates (ADCs) are designed to deliver potent cytotoxic agents into tumor tissues. During the last two decades, a plethora of ADCs have been successfully developed and used for several indications, including hematologic and solid tumors. In this work, we systematically reviewed the progress in ADC development for the treatment of HNC. Methods: This review was registered in PROSPERO database. A comprehensive search was conducted following PRISMA guidelines and using PubMed, Scopus and Web of Science database. Results: In total, 19 studies were included. Due to the significant heterogeneity of the outcome measures, meta-analysis was not performed, and data were summarized in tables. HNC results are poorly represented in the cohorts of completed clinical trials; published data are mostly focused on safety evaluation rather than efficacy of ADCs. Conclusions: Although several novel agents against a wide range of different antigens were investigated, showing promising results at a preclinical level, most of the targets reported in this review are not specific for HNC; hence, the development of ADCs tailored for the HNC phenotype could open up new therapeutic perspectives. Moreover, the results from the present systematic review call attention to how limited is the application of current clinical trials in HNC. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates for the Treatment of Cancer)
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