AI Article Synopsis
- Pyrrolobenzodiazepine dimers are a new type of drug used in antibody-drug conjugates (ADCs) that aim to effectively target and kill cancer cells.
- Tesirine (SG3249) was specifically designed for strong anti-tumor effects while maintaining suitable properties for production and linking to antibodies—a process enhanced by a special cleavable linker.
- Rova-T, created by linking tesirine with the antibody rovalpituzumab, is currently being tested as a treatment for small cell lung cancer.
Article Abstract
Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics. One of the reactive imines was capped with a cathepsin B-cleavable valine-alanine linker. A robust synthetic route was developed to allow the production of tesirine on clinical scale, employing a flexible, convergent strategy. Tesirine was evaluated both in stochastic and engineered ADC constructs and was confirmed as a potent and versatile payload. The conjugation of tesirine to anti-DLL3 rovalpituzumab has resulted in rovalpituzumab-tesirine (Rova-T), currently under evaluation for the treatment of small cell lung cancer.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5108040 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.6b00062 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The potential of antibody-drug conjugates for effective therapy in diffuse large B-cell lymphoma.
Expert Opin Biol Ther
January 2025
OU Stephenson Cancer Center, Oklahoma City.
Introduction: Antibody-drug conjugates (ADCs) are a rapidly evolving class of anti-cancer drugs with a significant impact on management of hematological malignancies including diffuse large B-cell lymphoma (DLBCL). ADCs combine a cytotoxic drug (a.k.
View Article and Find Full Text PDFAdvances in DLL3-targeted therapies for small cell lung cancer: challenges, opportunities, and future directions.
Front Oncol
December 2024
Taylor's University, Subang Jaya, Selangor, Malaysia.
Small cell lung cancer (SCLC) remains one of the most aggressive and challenging malignancies to treat, with limited therapeutic options and poor outcomes. Recent advances in understanding SCLC biology have identified Delta-like ligand 3 (DLL3) as a promising target for novel therapies. This review explores the evolving landscape of DLL3-targeted therapies in SCLC, examining their mechanistic basis, preclinical promise, and clinical development.
View Article and Find Full Text PDFLoncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single-centre, single-arm, phase 2 trial.
Lancet Haematol
January 2025
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: Preliminary data suggest promising activity of loncastuximab tesirine in follicular lymphoma, and synergistic activity between rituximab-induced cytotoxicity and loncastuximab tesirine. In this study, we evaluated loncastuximab tesirine combined with rituximab for second-line and later treatment of follicular lymphoma.
Methods: We did a single-arm, investigator-initiated, phase 2 trial at Sylvester Comprehensive Cancer Center in Miami, FL, USA.
Loncastuximab tesirine in previously treated diffuse large B-cell lymphoma: A plain language summary of the LOTIS-2 study.
Future Oncol
November 2024
Department of Biomedical Sciences, Humanitas University, & Department of Oncology & Hematology, Humanitas Research Hospital-IRCCS, Milano, Italy.
What Is This Summary About?: This article provides a plain-language summary of the results of a clinical trial called the LOTIS-2 study.The LOTIS-2 study included 145 participants with an aggressive type (one that forms, grows, or spreads quickly) of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (a type of blood cancer), or DLBCL for short, whose disease came back or did not respond after 2 or more previous treatments. The LOTIS-2 study was conducted from August 2018 to September 2022.
View Article and Find Full Text PDFUnderstanding how CD19 expression levels impact the response to loncastuximab tesirine: a plain language summary.
Future Oncol
November 2024
ADC Therapeutics, Murray Hill, NJ, USA.
What Is This Summary About?: In this article, we summarize results from a clinical study called LOTIS-2, in which researchers looked at patients with a type of blood cancer called diffuse large B-cell lymphoma, or DLBCL for short. Patients received the drug loncastuximab tesirine, or Lonca for short, which targets a marker on the surface of tumor cells called CD19.Patient information from the LOTIS-2 study, other studies of Lonca, and information from scientific publications was used to develop a quantitative systems pharmacology (QSP) model, which can predict how Lonca works in the body.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!