Umbilical cord blood (CB) can serve as an alternative graft for patients lacking a matched related donor, yet intrinsically low cell doses leading to delayed engraftment and graft failure severely restrict wider use of this valuable resource. Hence, the central hypothesis of Project 1 is that CB progenitors expanded ex vivo on mesenchymal stem cells (MSCs) will provide more rapid hematopoietic reconsititution, as well as less engraftment failure, than unmanipulated CB cells. Indeed, the CB mononuclear cell/MSC co-culture system we have developed should avoid the significant CD34+ cell losses we experienced in earlier liquid suspension culture studies and, because it provides a surrogate niche for the propagation of CB progenitors, should yield improved CB cell expansion overall. This prediction will be tested in a phase 1 clinical trial in patients undergoing CB transplantation for hematologic malignancies (Aim 1.1), coupled with mechanistic studies to determine if optimal expansion is inhibited by specific CB

Public Health Relevance

Slow recovery of white blood cells to fight infection, platelets to prevent bleeding and red cells to carry oxygen represent major obstacles to wider use of cord blood transplantation. Project 1 seeks to overcome these barriers by improving the expansion of cord blood cells, and by directing their migration to the bone marrow, before their transplantation into patients. If successful, this strategy will improve the survival of cord blood transplant patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA148600-03
Application #
8567110
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$514,206
Indirect Cost
$121,215
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Sekine, Takuya; Marin, David; Cao, Kai et al. (2016) Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation. Blood 128:297-312
Patel, Shabnum; Lam, Sharon; Cruz, Conrad Russell et al. (2016) Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-Naïve Donors and Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 22:536-41
Torikai, Hiroki; Mi, Tiejuan; Gragert, Loren et al. (2016) Genetic editing of HLA expression in hematopoietic stem cells to broaden their human application. Sci Rep 6:21757
Tripathi, Satyendra C; Peters, Haley L; Taguchi, Ayumu et al. (2016) Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proc Natl Acad Sci U S A 113:E1555-64
Patel, Shabnum; Jones, R Brad; Nixon, Douglas F et al. (2016) T-cell therapies for HIV: Preclinical successes and current clinical strategies. Cytotherapy 18:931-42
Bollard, Catherine M; Heslop, Helen E (2016) T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood 127:3331-40
Thompson, Philip A; Perera, Travis; Marin, David et al. (2016) Double umbilical cord blood transplant is effective therapy for relapsed or refractory Hodgkin lymphoma. Leuk Lymphoma 57:1607-15
Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A et al. (2016) Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. J Allergy Clin Immunol 137:1498-1505.e1
Kebriaei, Partow; Singh, Harjeet; Huls, M Helen et al. (2016) Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest 126:3363-76
Spielmann, Guillaume; Bollard, Catherine M; Kunz, Hawley et al. (2016) A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy. Sci Rep 6:25852

Showing the most recent 10 out of 86 publications