Leland Stanford Junior University

University of California

Judith A Shizuru

Irving L Weissman

Akanksha Chhabra

Kipp Andrew Weiskopf

Peter Schnorr

Aaron Michael Ring

Susan Sweeney Prohaska

Agnieszka Czechowicz

Benson M George

Aaron Logan

Anne Le

Kenneth Weinberg

Hye Sook Kwon

Christopher Dvorak

Maria-Grazia Roncarolo

Robertson Parkman

Morton J Cowan

Janel Long Boyle

Rajni Agarwal

Joseph H Lin

Wendy Pang

Weissman Irving L L

The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection.

Non-genotoxic conditioning regimen for stem cell transplantation

The present invention provides a clinically applicable method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring radiotherapy or chemotherapy, and without development of GVHD or graft rejection. Aspects of the present invention are based on the discovery that the depletion of the endogenous stem cell niche facilitates efficient engraftment of stem cells into that niche. In particular, the present invention combines the use of selective ablation of endogenous stem cells with a combination of antibodies specific for CD117, and agents that modulate immunoregulatory signaling pathways, e.g. agonists of immune costimulatory molecules, in combination with the administration to the recipient of exogenous stem cells, resulting in efficient, long-term engraftment, even in immunocompetent recipients.

Engraftment of stem cells with a combination of an agent that targets stem cells and modulation of immunoregulatory signaling

Methods are provided for targeting cells for depletion, including without limitation tumor cells, in a regimen comprising contacting the targeted cells with a combination of agents that modulate immunoregulatory signaling. Immunoregulatory modulating agents include (i) an agent that blockades CD47 activity; and (ii) an agent that agonizes an immune costimulatory molecule, e.g. CD137. The regimen may further comprise an agent that specifically binds to the target cell, e.g. an antibody or biologically active fragment or derivative thereof. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single immunoregulatory modulating agent is used; and the effect may be synergistic relative to a regimen in which a single immunoregulatory modulating agent is used.

Enhanced depletion of targeted cells with CD47 blockade and an immune costimulatory agonist

The present invention provides clinical evidence for a method of stem cell transplantation that facilitates engraftment and reconstitutes immunocompetence of the recipient without requiring myeloablative conditioning.

Hematopoietic stem cell engraftment

Substantially enriched mammalian lung endothelial and epithelial progenitor cell populations are provided. Methods are provided for the isolation and in vivo differentiation of such lung progenitor cells. The progenitor cells are obtained from lung tissue, including fetal and adult tissues. The cells are useful in transplantation, for experimental evaluation, and as a source of lineage and cell specific products, including mRNA species useful in identifying genes specifically expressed in these cells, and as targets for the discovery of factors or molecules that can affect them.

Lung epithelial progenitor cells

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Palo Alto, CA, United States of America

Judith A Shizuru