Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives

Lozza, Irene; Torres-Suárez, Ana Isabel; Fraguas-Sánchez, Ana Isabel

doi:10.3390/pharmaceutics13101705

Cited by 13 publications

(8 citation statements)

References 151 publications

(156 reference statements)

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“…Two ADC using this technology have entered clinical trials. Upifitomab rilsodotum 135,136 uses MMAF as the warhead; in a Phase 1/2 trial, it did not show improvement over control against platinum-resistant ovarian cancer. A second ADC, XMT 2056, uses the same platform but uses an STING agonist as the warhead.…”

Section: Adc Basicsmentioning

confidence: 98%

The Evolving Landscape of Antibody–Drug Conjugates: In Depth Analysis of Recent Research Progress

Sasso,

Tenchov,

Bird

et al. 2023

Bioconjugate Chem.

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Antibody–drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows for higher doses of the cytotoxic drug to be administered, potentially increasing efficacy. They are currently among the most promising drug classes in oncology, with efforts to expand their application for nononcological indications and in combination therapies. Here we provide a detailed overview of the recent advances in ADC research and consider future directions and challenges in promoting this promising platform to widespread therapeutic use. We examine data from the CAS Content Collection, the largest human-curated collection of published scientific information, and analyze the publication landscape of recent research to reveal the exploration trends in published documents and to provide insights into the scientific advances in the area. We also discuss the evolution of the key concepts in the field, the major technologies, and their development pipelines with company research focuses, disease targets, development stages, and publication and investment trends. A comprehensive concept map has been created based on the documents in the CAS Content Collection. We hope that this report can serve as a useful resource for understanding the current state of knowledge in the field of ADCs and the remaining challenges to fulfill their potential.

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Section: Adc Basicsmentioning

confidence: 98%

The Evolving Landscape of Antibody–Drug Conjugates: In Depth Analysis of Recent Research Progress

Sasso,

Tenchov,

Bird

et al. 2023

Bioconjugate Chem.

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“…Notably, the FDA approval of mertansine (DM1) in 2013, which incorporates maytansine as a payload into trastuzumab emtansine (Kadcyla®), has proven successful in the treatment of advanced breast cancer 92 . Additionally, various analogs of maytansine, including DM4 (ravtansine/soravtansine), have shown promising potential as ADC payloads in clinical trials 93,94 …”

Section: Tubulin‐binding Sites and Mechanisms Of Action Of Mdasmentioning

confidence: 99%

“…92 Additionally, various analogs of maytansine, including DM4 (ravtansine/soravtansine), have shown promising potential as ADC payloads in clinical trials. 93,94 In 2014, Prota et al 95 determined the X-ray crystallography structure of maytansine bound to tubulin. Their findings unveiled a distinct binding site for maytansine, adjacent to the vinca alkaloids binding site.…”

Section: Maytansine Sitementioning

confidence: 99%

Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies

Wang,

Gigant,

Zheng

et al. 2023

MedComm – Oncology

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Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and cell mitosis/division. They are validated targets for disease treatment, notably hematological cancers and solid tumors. Microtubule‐targeting agents (MTAs) exert their effects by modulating microtubule dynamics, impeding cell proliferation, and promoting cell death. Recent advances in structural biology have unveiled novel perspectives for investigating multiple binding sites and mechanisms of action used by MTAs. In this review, we first provide an overview of the intricate structure and dynamics of microtubules. Then we explore the seven binding sites and the three primary strategies (stabilization, destabilization, and degradation) harnessed by MTAs. Furthermore, we introduce the emerging domain of microtubule‐targeting degraders, exemplified by PROteolysis TArgeting Chimeras and small‐molecule degraders, which enable precise degradation of specific microtubule‐associated proteins implicated in cancer pathogenesis. Additionally, we discuss the promising realm of precision‐targeted approaches, including antibody–drug conjugates and the utilization of photopharmacology in MTAs. Lastly, we provide a comprehensive overview of the clinical applications of microtubule‐targeting therapies, assessing their efficacy and current challenges. We aim to provide a global picture of MTAs development as well as insights into the microtubule‐targeting drug discovery for cancer treatment.

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“…ADCs containing SN-38 with a tolerable safety profile have been successfully developed. Moreover, some monoclonal antibodies exert an anticancer effect per se, such as trastuzumab, potentiating the overall tumor growth inhibition [ 41 ]. In fact, breast cancer, is one of the tumors where most antibody–drug conjugates have been developed and approved.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic

Fraguas-Sánchez

Lozza

Torres-Suárez

2022

Cancers

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Breast cancer is one of the most frequently diagnosed tumors and the second leading cause of cancer death in women worldwide. The use of nanosystems specifically targeted to tumor cells (active targeting) can be an excellent therapeutic tool to improve and optimize current chemotherapy for this type of neoplasm, since they make it possible to reduce the toxicity and, in some cases, increase the efficacy of antineoplastic drugs. Currently, there are 14 nanomedicines that have reached the clinic for the treatment of breast cancer, 4 of which are already approved (Kadcyla®, Enhertu®, Trodelvy®, and Abraxane®). Most of these nanomedicines are antibody–drug conjugates. In the case of HER-2-positive breast cancer, these conjugates (Kadcyla®, Enhertu®, Trastuzumab-duocarmycin, RC48, and HT19-MMAF) target HER-2 receptors, and incorporate maytansinoid, deruxtecan, duocarmicyn, or auristatins as antineoplastics. In TNBC these conjugates (Trodelvy®, Glembatumumab-Vedotin, Ladiratuzumab-vedotin, Cofetuzumab-pelidotin, and PF-06647263) are directed against various targets, in particular Trop-2 glycoprotein, NMB glycoprotein, Zinc transporter LIV-1, and Ephrin receptor-4, to achieve this selective accumulation, and include campthotecins, calicheamins, or auristatins as drugs. Apart from the antibody–drug conjugates, there are other active targeted nanosystems that have reached the clinic for the treatment of these tumors such as Abraxane® and Nab-rapamicyn (albumin nanoparticles entrapping placlitaxel and rapamycin respectively) and various liposomes (MM-302, C225-ILS-Dox, and MM-310) loaded with doxorubicin or docetaxel and coated with ligands targeted to Ephrin A2, EPGF, or HER-2 receptors. In this work, all these active targeted nanomedicines are discussed, analyzing their advantages and disadvantages over conventional chemotherapy as well as the challenges involved in their lab to clinical translation. In addition, examples of formulations developed and evaluated at the preclinical level are also discussed.

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Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives

Cited by 13 publications

References 151 publications

The Evolving Landscape of Antibody–Drug Conjugates: In Depth Analysis of Recent Research Progress

The Evolving Landscape of Antibody–Drug Conjugates: In Depth Analysis of Recent Research Progress

Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies

Actively Targeted Nanomedicines in Breast Cancer: From Pre-Clinal Investigation to Clinic

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