Abstract 224: Antibody-drug conjugates (ADCs) of a new class of N-10 amino linked DNA alkylating indolino-benzodiazepines (IGNs)

Author(s):  
Michael L. Miller ◽  
Emily E. Reid ◽  
Katie E. Archer ◽  
Luke Harris ◽  
Erin K. Maloney ◽  
...  
2016 ◽  
Vol 15 (8) ◽  
pp. 1870-1878 ◽  
Author(s):  
Michael L. Miller ◽  
Nathan E. Fishkin ◽  
Wei Li ◽  
Kathleen R. Whiteman ◽  
Yelena Kovtun ◽  
...  

2019 ◽  
Author(s):  
Michael L. Miller ◽  
Emily E. Reid ◽  
Katie E. Archer ◽  
Luke Harris ◽  
Erin K. Maloney ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Carmen Criscitiello ◽  
Stefania Morganti ◽  
Giuseppe Curigliano

AbstractAntibody–drug conjugates (ADCs) are a relatively new class of anticancer agents designed to merge the selectivity of monoclonal antibodies with cell killing properties of chemotherapy. They are commonly described as the “Trojan Horses” of therapeutic armamentarium, because of their capability of directly conveying cytotoxic drug (payloads) into the tumor space, thus transforming chemotherapy into a targeted agent. Three novel ADCs have been recently approved, i.e., trastuzumab deruxtecan, sacituzumab govitecan and enfortumab vedotin, respectively, targeting HER2, Trop2 and Nectin4. Thanks to progressive advances in engineering technologies these drugs rely on, the spectrum of diseases sensitive to these drugs as well as their indications are in continuous expansion. Several novel ADCs are under evaluation, exploring new potential targets along with innovative payloads. This review aims at providing a summary of the technology behind these compounds and at presenting the latest ADCs approved in solid tumors, as well as at describing novel targets for ADCs under investigation and new strategies to optimize their efficacy in solid tumors.


Author(s):  
Semir Vranic ◽  
Zoran Gatalica

Antibody-drug conjugates (ADCs) represent a new class of highly potent antineoplastic drugs built by attaching a small molecule of an anticancer drug (payload) or another therapeutic agent to an antibody recognizing an epitope on the targeted cells. Trophoblast cell-surface antigen-2 (Trop-2) was originally described in trophoblasts and fetal tissues, but subsequently, its overexpression has been demonstrated in various solid malignancies. Sacituzumab govitecan, a conjugate of anti-Trop-2 antibody and SN-38 payload (an active metabolite of irinotecan), is the first in the class that has been clinically validated and approved by the Food and Drug Administration for the treatment of metastatic triple-negative breast (2020) and urothelial carcinomas (2021). In the current review, we summarize and critically appraise the most recent advances with Sacituzumab govitecan, emphasizing the predictive biomarker analysis.


2018 ◽  
Vol 30 (1) ◽  
pp. 200-209 ◽  
Author(s):  
Anokha S. Ratnayake ◽  
Li-ping Chang ◽  
L. Nathan Tumey ◽  
Frank Loganzo ◽  
Joseph A. Chemler ◽  
...  

2019 ◽  
Vol 10 (03) ◽  
pp. 140-141
Author(s):  
Alexander Kretzschmar

Die Therapielandschaft des metastasierten Urothelkarzinoms hat sich seit der Zulassung der ersten Immun-Checkpoint-Inhibitoren verändert. Die neuen Therapien sind deutlich effektiver, allerdings erreichen die Responseraten der neuen Therapien nur bis zu etwa 30 %, beklagte Prof. Matthew Milowsky, Chapel Hill/USA, auf einer Oral Abstract Session auf dem ASCO-GU. In San Francisco gaben erste Vorträge und Poster bereits einen Einblick, wovon diejenigen Patienten profitieren könnten, die auf die etablierten Chemotherapien und die neuen Immuntherapien nicht ansprechen. Manche Onkologen sprechen bereits von der „Post-Checkpoint-Ära”. Als Kandidaten werden vor allem Antikörper-Wirkstoff-Konjugate (antibody-drug conjugates; ADC) gehandelt – und zwar nicht nur zur Therapie des metastasierten Blasenkarzinoms.


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