Article
Chemistry, Analytical
Hoda E. Mohamed, Medhat A. Al-Ghobashy, Samah S. Abbas, Shereen A. Boltia
Summary: Antibody-drug conjugates (ADCs) are innovative biopharmaceuticals that combine potent cytotoxic drugs with monoclonal antibodies to target cancer cells. This study investigated the stability and degradation of two ADCs, POLA and SGN-35, under various stress conditions. Different analytical techniques, including SE-HPLC, DLS, HIC-HPLC, RP-HPLC, and ELISA, were used to quantify degradation products, monitor aggregation and fragmentation, determine drug antibody ratio, and test binding activity. The results demonstrated the importance of using multiple techniques to evaluate the quality and stability of ADCs.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Review
Biochemistry & Molecular Biology
Jana Mihalyova, Katarina Hradska, Tomas Jelinek, Benjamin Motais, Piotr Celichowski, Roman Hajek
Summary: In recent years, treatment approaches for B-cell lymphoma subtypes and CLL have shifted towards more targeted therapies, including mAbs, bsAbs, ADCs, and CAR-T cell therapy. TCEs, a subclass of bsAbs, have shown similar mechanisms to CAR-T cell therapy but without the need for prior T-cell manipulation. Anti-CD20xCD3 TCEs have demonstrated promising efficacy in various lymphoma subtypes, with ADCs targeting different B-cell antigens showing effectiveness in combination with other treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Louise Conilh, Lenka Sadilkova, Warren Viricel, Charles Dumontet
Summary: Antibody-drug conjugates (ADCs) combine monoclonal antibodies' selectivity with cytotoxic payloads, and recent success in ADC development includes unconventional payloads with differentiated mechanisms of action. Future developments in the ADC field will focus on diversification of payloads, as seen in the growing number of preclinical and clinical unconventional payload-conjugated ADCs. This review provides an overview of validated, forgotten, and newly developed payloads with different mechanisms of action.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Ryan D. Lyski, Lauren B. Bou, Uland Y. Lau, David W. Meyer, Julia H. Cochran, Nicole M. Okeley, Kim K. Emmerton, Francisco Zapata, Jessica K. Simmons, Esther S. Trueblood, David J. Ortiz, Margo C. Zaval, Katie M. Snead, Steven Jin, Lauren M. Farr, Maureen C. Ryan, Peter D. Senter, Scott C. Jeffrey
Summary: The developed ADC with the novel camptothecin drug-linker showed high activity and tolerance, with improved drug loading capability and stability. It demonstrated significant efficacy in various cancer cells and tumor models, making it a promising option for targeted drug delivery.
MOLECULAR CANCER THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Michael Z. Liao, Dan Lu, Matts Kagedal, Dale Miles, Divya Samineni, Stephanie N. Liu, Chunze Li
Summary: ADCs combine antibody specificity with chemical cytotoxicity and are a rapidly evolving area of oncology drug development, with promise for improving cancer treatment. There are nine ADCs on the market, over half of which gained FDA approval since 2019, but their therapeutic window is relatively narrow compared to other oncology drugs. Strategies such as body weight cap dosing, treatment duration capping, dose schedule optimization, response-guided dosing recommendations, and randomized dose-finding are being utilized to broaden the therapeutic window and maximize safety and efficacy for next-generation ADCs.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Chemistry, Multidisciplinary
Thomas A. King, Stephen J. Walsh, Mia Kapun, Thomas Wharton, Sona Krajcovicova, Melanie S. Glossop, David R. Spring
Summary: Numerous antibody-drug conjugate (ADC) linker technologies are available for synthesizing ADCs with even integer drug-to-antibody ratios (DARs) (typically 2, 4, or 8). However, synthesizing ADCs with odd integer DARs is more challenging. This study reports the synthesis of ADCs loaded with a single warhead using TetraDVP linkers, which can simultaneously re-bridge all four interchain disulfides of an IgG1 antibody.
CHEMICAL COMMUNICATIONS
(2023)
Article
Oncology
Fulvio Massaro, Nathalie Meuleman, Dominique Bron, Marie Vercruyssen, Marie Maerevoet
Summary: This retrospective study evaluated the efficacy of a combination of brentuximab vedotin and pembrolizumab as a bridge treatment to autologous stem cell transplantation (ASCT) in relapsed/refractory Hodgkin lymphoma (HL) patients. The results showed that this combination therapy is highly effective for high-risk patients.
Review
Oncology
Mo Wu, Wei Huang, Nan Yang, Yanyong Liu
Summary: Chemotherapy is criticized for its non-selective toxicity and drug resistance. Combination therapy, such as drug conjugates, has been developed to improve clinical efficacy. Compared to antibody-drug conjugates, peptide-drug conjugates have advantages but also face limitations in development.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Cynthia Mark, Jin Sun Lee, Xiaojiang Cui, Yuan Yuan
Summary: Antibody drug conjugates (ADCs) combine monoclonal antibodies with cytotoxic drugs for selective delivery to cancer cells, optimizing treatment effectiveness. ADC research has significantly impacted breast cancer management, providing valuable options. However, important questions remain, such as drug sequencing and overcoming resistance mechanisms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jesus Fuentes-Antras, Sofia Genta, Abi Vijenthira, Lillian L. Siu
Summary: Antibody-drug conjugates (ADCs) have been approved as anticancer drugs for both solid and hematological malignancies, but only a few have shown survival improvements over standard treatment. The most promising partners for ADCs are those that have additive or synergistic effects on tumor cells without overlapping toxicities. Co-administration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents, and immune checkpoint inhibitors (ICIs) are active candidates. The next generation of ADCs, with tumor-specific targets, improved conjugation technologies, and novel linkers and payloads, brings hope for combinatorial approaches.
Article
Chemistry, Multidisciplinary
Syeda Warisul Fatima, Sunil K. Khare
Summary: ADCs are a new therapeutic approach that combines chemotherapy and immunotherapy, delivering cytotoxic molecules to cancer cells through monoclonal antibodies. Research reviews how to enhance ADCs efficiency and the promising prospects of antibody conjugated nanoparticles (ACNPs) in targeted drug delivery to cancer cells.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Biochemistry & Molecular Biology
Rita Khoury, Khalil Saleh, Nadine Khalife, Mohamad Saleh, Claude Chahine, Rebecca Ibrahim, Axel Lecesne
Summary: The treatment of cancer patients has changed significantly with the introduction of monoclonal antibodies, immune-checkpoint inhibitors, bispecific antibodies, and T-cell therapy. Antibody-drug conjugates (ADCs) have also revolutionized cancer treatment. This review summarizes the clinical data supporting the approval of ADCs such as T-DM1, T-DXd, SG, and EV, and discusses the mechanisms of resistance to ADCs and potential strategies to overcome it.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Ahmad Hussain, Armin Grimm, Wenjie Sheng, Chaoyu Zhang, Marwah Al-Rawe, Karen Braeutigam, Mobarak Abu Mraheil, Felix Zeppernick, Ivo Meinhold-Heerlein
Summary: Antibodies have revolutionized cancer treatment with their unique ability to recognize specific antigens and various therapeutic mechanisms. Modification techniques have allowed for the development of new antibody-conjugate-based diagnostic and therapeutic agents, but overcoming the heterogeneity generated by bioconjugation approaches remains a challenge. This review highlights enzyme-based site-specific conjugation methods to improve antibody properties.
Review
Pharmacology & Pharmacy
Zheng Su, Dian Xiao, Fei Xie, Lianqi Liu, Yanming Wang, Shiyong Fan, Xinbo Zhou, Song Li
Summary: ADCs are gradually revolutionizing clinical cancer therapy, and the linker molecule plays a crucial role in determining their efficacy and safety. An ideal linker should release the cytotoxic payload specifically in the tumor to avoid off-target toxicity. Recent research progress in novel linkers for ADCs has been significant, aiming to improve therapeutic outcomes and minimize adverse effects.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Analytical
Jennifer L. Bonetti, Saer Samanipour, Arian C. van Asten
Summary: Differentiating positional isomers is a challenge for forensic laboratories, and a rapid and accurate identification method is needed. In this study, chemometric analysis of DART-ToF data was used, and the Random Forest algorithm was found to be efficient in distinguishing NPS positional ring isomers.
ANALYTICAL CHEMISTRY
(2022)