Antibody targeting KIT as pretransplantation conditioning in immunocompetent mice

Xingkui Xue, Nancy K. Pech, W. Christopher Shelley, Edward F. Srour, Mervin C. Yoder, Mary C. Dinauer

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Inherited hematologic defects that lack an in vivo selective advantage following gene correction may benefit from effective yet minimally toxic cytoreduction of endogenous hematopoietic stem cells (HSCs) prior to transplantation of gene-modified HSCs. We studied the efficacy of administering a novel sequential treatment of parenteral ACK2, an antibody that blocks KIT, followed by low-dose irradiation (LD-IR) for conditioning of wild-type and X-linked chronic granulomatous disease (X-CGD) mice. In wild-type mice, combining ACK2 and LD-IR profoundly decreased endogenous competitive long-term HSC repopulating activity, and permitted efficient and durable donor-derived HSC engraftment after congenic transplantation. ACK2 alone was ineffective. The combination of ACK2 and LD-IR was also effective conditioning in X-CGD mice for engraftment of X-CGD donor HSCs transduced ex vivo with a lentiviral vector. We conclude that combining ACK2 with LD-IR is a promising approach to effectively deplete endogenous HSCs and facilitate engraftment of transplanted donor HSCs.

Original languageEnglish
Pages (from-to)5419-5422
Number of pages4
Issue number24
StatePublished - Dec 9 2010


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