Jenny Yeung, Aiyin Liao, Matthew Shaw, Soraia Silva, Winston Vetharoy, Diego Leon Rico, Ian Kirby, Francesca Zammarchi, Karin Havenith, Lolke de Haan, Patrick H van Berkel, Neil Sebire, Olumide K Ogunbiyi, Claire Booth, H Bobby Gaspar, Adrian J Thrasher, Kerry A Chester, Persis J Amrolia
Stem cell gene therapy and hematopoietic stem cell transplantation (SCT) and stem cell gene therapy require conditioning to ablate the recipient's hematopoietic stem cells (HSC) and create a niche for gene-corrected/donor HSCs. Conventional conditioning agents are non-specific, leading to off-target toxicities, resulting in significant morbidity and mortality. We developed tissue-specific anti-human CD45 antibody-drug conjugates (ADCs), using rat IgG2b anti-human CD45 antibody clones YTH24.5 and YTH54.12, conjugated to cytotoxic pyrrolobenzodiazepine (PBD) dimer payloads with cleavable (SG3249) or non-cleavable (SG3376) linkers...
March 27, 2024: Molecular Therapy