Cover Image

HDP-101, an anti-BCMA antibody-drug conjugate, safely delivers amanitin to induce cell death in proliferating and resting multiple myeloma cells

Despite major treatment advances in recent years, patients with multiple myeloma inevitably relapse. The RNA polymerase II complex has been identified as a promising therapeutic target in both proliferating and dormant cancer cells. Alpha-amanitin, a toxin so far without clinical application due to...

Full description

Saved in:
Bibliographic Details
Main Authors: Figueroa Vazquez, Vianihuini (Author) , Ko, Jonathan (Author) , Breunig, Christian (Author) , Baumann, Anja (Author) , Giesen, Nicola (Author) , Palfi, Aniko (Author) , Müller, Christoph (Author) , Lutz, Christian (Author) , Hechler, Torsten (Author) , Kulke, Michael (Author) , Müller-Tidow, Carsten (Author) , Krämer, Alwin (Author) , Goldschmidt, Hartmut (Author) , Pahl, Andreas (Author) , Raab, Marc-Steffen (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Molecular cancer therapeutics
Year: 2021, Volume: 20, Issue: 2, Pages: 367-378
ISSN:1538-8514
DOI:10.1158/1535-7163.MCT-20-0287
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1535-7163.MCT-20-0287
Verlag, lizenzpflichtig, Volltext: https://mct.aacrjournals.org/content/20/2/367
Get full text
Author Notes:Vianihuini Figueroa-Vazquez, Jonathan Ko, Christian Breunig, Anja Baumann, Nicola Giesen, Anikó Pálfi, Christoph Müller, Christian Lutz, Torsten Hechler, Michael Kulke, Carsten Müller-Tidow, Alwin Krämer, Hartmut Goldschmidt, Andreas Pahl, and Marc S. Raab
Description
Summary:Despite major treatment advances in recent years, patients with multiple myeloma inevitably relapse. The RNA polymerase II complex has been identified as a promising therapeutic target in both proliferating and dormant cancer cells. Alpha-amanitin, a toxin so far without clinical application due to high liver toxicity, specifically inhibits this complex. Here, we describe the development of HDP-101, an anti-B-cell maturation antigen (BCMA) antibody conjugated with an amanitin derivative. HDP-101 displayed high efficacy against both proliferating and resting myeloma cells in vitro, sparing BCMA-negative cells. In subcutaneous and disseminated murine xenograft models, HDP-101 induced tumor regression at low doses, including durable complete remissions after a single intravenous dose. In cynomolgus monkeys, HDP-101 was well tolerated with a promising therapeutic index. In conclusion, HDP-101 safely and selectively delivers amanitin to myeloma cells and provides a novel therapeutic approach to overcome drug resistance in this disease.
Item Description:Published online first: December 9, 2020
Gesehen am 08.09.2021
Physical Description:Online Resource
ISSN:1538-8514
DOI:10.1158/1535-7163.MCT-20-0287

Similar Items