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Review
. 2022 Feb 2;14(3):778.
doi: 10.3390/cancers14030778.

Antibody-Drug Conjugates as an Emerging Therapy in Oncodermatology

Clara Esnault  1   2 , David Schrama  2 , Roland Houben  2 , Serge Guyétant  1   3 , Audrey Desgranges  4 , Camille Martin  4 , Patricia Berthon  1 , Marie-Claude Viaud-Massuard  4   5 , Antoine Touzé  1 , Thibault Kervarrec  1   3 , Mahtab Samimi  1   6
Affiliations
Review

Antibody-Drug Conjugates as an Emerging Therapy in Oncodermatology

Clara Esnault et al. Cancers (Basel). .

Abstract

Antibody-drug conjugates (ADCs) are an emerging class of therapeutics, with twelve FDA- and EMA-approved drugs for hematological and solid cancers. Such drugs consist in a monoclonal antibody linked to a cytotoxic agent, allowing a specific cytotoxicity to tumor cells. In recent years, tremendous progress has been observed in therapeutic approaches for advanced skin cancer patients. In this regard, targeted therapies (e.g., kinase inhibitors) or immune checkpoint-blocking antibodies outperformed conventional chemotherapy, with proven benefit to survival. Nevertheless, primary and acquired resistances as well as adverse events remain limitations of these therapies. Therefore, ADCs appear as an emerging therapeutic option in oncodermatology. After providing an overview of ADC design and development, the goal of this article is to review the potential ADC indications in the field of oncodermatology.

Keywords: antibody–drug conjugates; cutaneous T-cell lymphoma and Merkel cell carcinoma; melanoma; oncodermatology; skin squamous cell carcinoma.

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Conflict of interest statement

A.D., C.M. and M.-C.V.-M. are employees of McSAF, who is the owner of the patent Adcitmer®. A.T., T.K. and M.S. filed this patent. T.K. is A.D.’s husband. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Design of an antibody–drug conjugate and recommended biological properties. Characteristic of antigen, antibody, linker–antibody attachment, linker, linker–payload attachment and payload are detailed. The antibody Fc part is implied in half-life and immunogenicity. The Fab part controls affinity and avidity to the targeted antigen.
Figure 2
Figure 2
Overview of ADC mode of action. 1. Binding of the ADC to the antigen expressed by the cancer cell. 2. Internalization of the ADC. 3. Degradation of the linker or antibody inside the lysosome induces the release of an active form of the payload. 4. The payload exerts cellular toxicity depending on its mode of action. 5. A bystander effect can occur.
Figure 3
Figure 3
ADC targets in oncodermatologic indications and implication of antigen expression in cancer aggressiveness. (A) Cutaneous T-cell lymphoma. (B) Melanoma. (C) Carcinoma: squamous cell carcinoma and Merkel cell carcinoma.
See this image and copyright information in PMC

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