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Abstract
In the last decade, antibody-drug conjugates (ADCs), normally formed by a humanized antibody and a small drug via a chemical cleavable or non-cleavable linker, have emerged as a potential treatment strategy in cancer disease. They allow to get a selective delivery of the chemotherapeutic agents at the tumor level, and, consequently, to improve the antitumor efficacy and, especially to decrease chemotherapy-related toxicity. Currently, nine antibody-drug conjugate-based formulations have been already approved and more than 80 are under clinical trials for the treatment of several tumors, especially breast cancer, lymphomas, and multiple myeloma. To date, no ADCs have been approved for the treatment of gynecological formulations, but many formulations have been developed and have reached the clinical stage, especially for the treatment of ovarian cancer, an aggressive disease with a low five-year survival rate. This manuscript analyzes the ADCs formulations that are under clinical research in the treatment of gynecological carcinomas, specifically ovarian, endometrial, and cervical tumors.
Highlights
A recent phase III study (NCT02631876) carried out in 366 patients with ovarian cancer demonstrated a clinical benefit of mirvetuximab soravtansine at doses of 6 mg/kg compared to chemotherapy
Named Humax® -TF, is an antibody-drug conjugate based on Monomethyl auristatin E (MMAE) linked, via cathepsin cleavable linker, to a monoclonal antibody targeting tissue factor (TF), a transmembrane receptor and cofactor for factor VII/FVIIa [33], expressed by fibroblasts and epithelial cells and overexpressed in many tumors [98], including ovarian tumors [99]
SC-004 is another pyrrolobenzodiazepine-based antibody drug conjugate that consists of a monoclonal antibody targeted to claudins 6 and 9 (CLDN6/9), tight junctional proteins, that are overexpressed in ovarian tumors [117], bound to a pyrrolobenzodiazepine dimer
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Several immunotherapeutic treatments, including immune checkpoint inhibitors and monoclonal antibodies, have been approved in the last few years for the treatment of gynecological malignancies, especially for uterine, cervical, and ovarian carcinomas, improving the therapeutic options of these diseases [5,6,7]. A particular case of interest is the use of monoclonal antibodies as they can be conjugated with antineoplastic agents This allows to get a selective delivery of the chemotherapeutic drug at the tumor level, and, to improve the antitumor efficacy. In the case of gynecological malignancies, there are no approved ADCs. many of them are under clinical trials, especially for the treatment of ovarian cancer [11]. This review will focus on the ADCs designed for the treatment of gynecological malignancies, for the treatment of endometrial, ovarian, and cervical, analyzing the formulations that have reached the clinical investigation
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