Antibody–Drug Conjugates for Cancer Therapy

Hafeez, Umbreen; Parakh, Sagun; Gan, Hui; Scott, Andrew

doi:10.3390/molecules25204764

Cited by 235 publications

(208 citation statements)

References 179 publications

(172 reference statements)

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“…This technological approach, called antibody–drug conjugate, aims to carry anticancer drugs to the tumor via mAbs produced specifically on the cancer cell surface antigen. In this way, a form of chemotherapy with increased efficiency and reduced side effects is provided [ 46 ]. Kadcyla is an antibody–drug conjugate approved by the FDA and EMA in 2013 for use in the treatment of HER2-positive metastatic breast cancer [ 47 ].…”

Section: Strategies In Cancer Immunotherapymentioning

confidence: 99%

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

2021

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Clinically, different approaches are adopted worldwide for the treatment of cancer, which still ranks second among all causes of death. Immunotherapy for cancer treatment has been the focus of attention in recent years, aiming for an eventual antitumoral effect through the immune system response to cancer cells both prophylactically and therapeutically. The application of nanoparticulate delivery systems for cancer immunotherapy, which is defined as the use of immune system features in cancer treatment, is currently the focus of research. Nanomedicines and nanoparticulate macromolecule delivery for cancer therapy is believed to facilitate selective cytotoxicity based on passive or active targeting to tumors resulting in improved therapeutic efficacy and reduced side effects. Today, with more than 55 different nanomedicines in the market, it is possible to provide more effective cancer diagnosis and treatment by using nanotechnology. Cancer immunotherapy uses the body’s immune system to respond to cancer cells; however, this may lead to increased immune response and immunogenicity. Selectivity and targeting to cancer cells and tumors may lead the way to safer immunotherapy and nanotechnology-based delivery approaches that can help achieve the desired success in cancer treatment.

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Section: Strategies In Cancer Immunotherapymentioning

confidence: 99%

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

2021

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“…More importantly, auristatins appeared as great payloads in antibody-drug conjugates (ADCs) [132]. The efficacy of ADCs to exploit antibodies to target specific molecules on tumor cells and selectively deliver otherwise highly toxic molecules [133] is evident by the fact that four compounds belonging to this class have recently been approved for the treatment of patients with cancer (Table 1) and over 20 other compounds are in clinical evaluation [134][135][136].…”

Section: Peptide Derivativesmentioning

confidence: 99%

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

et al. 2020

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The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.

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“…To date, ten antibody-drug conjugates (ADCs) have been approved by the Food and Drug Administration (FDA) with four also approved by the European Medicines Agency (EMA) ( Hafeez et al, 2020 ; Joubert et al, 2020 ). Recent approvals of Zynlonta™ (loncastuximab tesirine-lpyl), Trodelvy ® (sacituzumab govitecan-hziy), Polivy ® (polatuximab vendotin) Enhertu ® (trastuzumab deruxtecan), Adcetris ® (brentuximab vendotin), Kadcyla ® (ado-trastuzumab emtansine), and Besponsa ® (inotuzumab ozogamicin) have increased interest in expanding the applications of ADCs.…”

Section: Introductionmentioning

confidence: 99%

Linker Design Impacts Antibody-Drug Conjugate Pharmacokinetics and Efficacy via Modulating the Stability and Payload Release Efficiency

Su¹,

Zhang²

2021

Front. Pharmacol.

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The development of antibody-drug conjugates (ADCs) has significantly been advanced in the past decade given the improvement of payloads, linkers and conjugation methods. In particular, linker design plays a critical role in modulating ADC stability in the systemic circulation and payload release efficiency in the tumors, which thus affects ADC pharmacokinetic (PK), efficacy and toxicity profiles. Previously, we have investigated key linker parameters such as conjugation chemistry (e.g., maleimide vs. disulfide), linker length and linker steric hindrance and their impacts on PK and efficacy profiles. Herein, we discuss our perspectives on development of integrated strategies for linker design to achieve a balance between ADC stability and payload release efficiency for desired efficacy in antigen-expressing xenograft models. The strategies have been successfully applied to the design of site-specific THIOMABTM antibody-drug conjugates (TDCs) with different payloads. We also propose to conduct dose fractionation studies to gain guidance for optimal dosing regimens of ADCs in pre-clinical models.

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Antibody–Drug Conjugates for Cancer Therapy

Cited by 235 publications

References 179 publications

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

A Review on Cancer Immunotherapy and Applications of Nanotechnology to Chemoimmunotherapy of Different Cancers

Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

Linker Design Impacts Antibody-Drug Conjugate Pharmacokinetics and Efficacy via Modulating the Stability and Payload Release Efficiency

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