학술논문
A Single Dose of CD117 Antibody Drug Conjugate Enables Autologous Gene-Modified Hematopoietic Stem Cell Transplant (Gene Therapy) in Nonhuman Primates
Document Type
Article
Author
Tisdale, John F.; Donahue, Robert E.; Uchida, Naoya; Pearse, Bradley R; McDonough, Sean M; Proctor, Jennifer L; Krouse, Allen; Linde, Nathaniel S.; Bonifacino, Aylin C.; Panwar, Rajiv; Sarma, Ganapathy N.; Kien, Lena; Latimer, Kellie; Dushime, Junia; Hyzy, Sharon L.; Brooks, Melissa L.; Palchaudhuri, Rahul; Li, Qing; Sawant, Pranoti; McDonagh, Charlotte F; Boitano, Anthony E.; Cooke, Michael P.
Source
Blood; November 2019, Vol. 134 Issue: 1, Number 1 Supplement 1 p610-610, 1p
Subject
Language
ISSN
00064971; 15280020
Abstract
Autologous hematopoietic stem cell transplantation (Auto-HSCT) with gene-modification techniques represents a potential cure for multiple genetic blood diseases. Despite its broad curative potential, auto-gene modified HSCT is currently limited due to morbidity/mortality from cytotoxic chemotherapy-based conditioning, including risks of secondary malignancies, organ toxicity, and infertility. To overcome these limitations, we have developed antibody drug conjugates (ADC) targeting CD117 (C-KIT) to specifically deplete the hematopoietic stem and progenitor cells (HSPC) prior to auto-gene modified HSCT. We have previously shown that the anti-CD117 ADC is highly effective at killing human CD117+ cells in vitroand in vivo(Pearse et al., Blood 2018 132:3314). To validate CD117 as an appropriate antigen for targeted ADC-mediated depletion prior to HSCT, we developed an optimized non-human primate (NHP) tool anti-CD117 ADC and evaluated it in an auto-gene modified HSCT in the rhesus macaque model.