Conditioning for Stem Cell Transplants

Patients with hematological malignancies or sickle cell disease often benefit from being transplanted with stem cells that can regenerate a normal hematopoietic system.  To improve patient tolerability and safety we are developing strategies to replace the harsh conditioning regimens, e.g. chemotherapy and irradiation, that are needed prior to transplantation.

(Dr. Steve Persaud, Peter Ruminski, Julie Ritchey)

 
DrawImpacts_Animation_purple_web2.gif
arrow3Grey.png
 
Conditioning for Stem Cell Transplants_figure.png
 

Before receiving a transplant patients undergo radiation and/or chemotherapy both to destroy tumor cells and to eliminate many of the native hematopoietic cells in the bone marrow.

 

This conditioning provides physical “space” in the bone marrow for the incoming donor cells to occupy as they proliferate and establish a strong-hold, i.e., become engrafted.  There they regenerate a donor-derived immune system composed of all the normal hematopoietic and immune cells.  We are using mouse models to explore the use of antibody drug conjugates alone or in combination with other treatments to establish engraftment without either irradiation or chemotherapy.  Some of these treatments involve the use of proprietary molecules generated by our medicinal chemists. These methodologies will later be used in patient studies at Washington University.

We also collaborate with other academic or industry partners using their proprietary molecules to discern whether they have the potential to open up bone marrow space.

 

 Key Publications

  • Persaud SP, Ritchey JK, Choi J, Ruminski PG, Cooper ML, Rettig MP, DiPersio JF. Antibody-drug conjugates targeting CD45 plus Janus kinase inhibitors effectively condition for allogeneic hematopoietic stem cell transplantation. Journal of Clinical Investigation. https://www.jci.org/articles/view/145501/pdf

  • Persaud SP, Ritchey JK, Kim S, Lim S, Ruminski PG, Cooper ML, Rettig MP, Choi J,  DiPersio JF. Antibody-Drug Conjugates Plus Janus Kinase Inhibitors Enable MHC Mismatched Allogeneic Hematopoietic Stem Cell Transplantation. J Clin Invest 2021 Dec 15;131(24):e145501

  • Persaud SP, Yelamali AR, Ritchey JK, DiPersio JF.  Conditioning with anti-CD47 and anti-CD117 plus JAK inhibition enables toxic payload-free allogeneic transplantation.  Blood Adv. 2024 Sep 10;8(17):4502-4506. doi: 10.1182/bloodadvances.2023012457.PMID: 38968137 No abstract available.

  • Yelamali AR, Chendamarai E, Ritchey JK, Rettig MP, DiPersio JF, Persaud SP.  Streptavidin-drug conjugates streamline optimization of antibody-based conditioning for hematopoietic stem cell transplantation.  bioRxiv. 2024 Feb 12:2024.02.12.579199. doi: 10.1101/2024.02.12.579199.PMID: 38405731 Free PMC article. Preprint.