QMS Technology to Deplete T Cell Alloreactivity

Project: Research project

Description

DESCRIPTION (provided by applicant): Allogeneic hematopoietic stem ceil transplantation remains the only curative option for many patients with hematological malignancies. Graft-versus-host disease (GvHD) is a major limitation to transplantation of hematopoeitic cells across histocompatibility barriers, and effectively limits transplantation to a minority of patients who would benefit from treatment. Extensive T cell depletion of the donor graft can eliminate GvHD. A significant consequence of T cell depletion, however, is a profound and long-lasting T cell immunodeficiency state post-transplant resulting in severe opportunistic viral and fungal infections that significantly limit survival. The adoptive infusion of mature, memory T cells post-transplant may offer protection against opportunistic infection, and shorted the period of immunodeficiency until successful immune reconstitution occurs. The success of this strategy in reducing mortality following T cell depleted transplants, however, will depend on the selective removal of alloreactive T cells that mediate GvHD, while retaining a high repertoire of memory T cells capable of reacting to viral and third party antigens. Although a number of methods have been investigated, the extent of depleting alloreactive T cell has been limited only to =3 log depletion of alloreactive T cells while retaininq >80% of third party reactivity. The technology developed in this proposal should greatly facilitate the development of clinical trials of adoptive donor T cell therapy to improve immune function following T-cell-depleted mismatched stem cell transplants.
StatusFinished
Effective start/end date5/1/044/30/10

Funding

  • National Institutes of Health: $587,422.00
  • National Institutes of Health: $595,781.00
  • National Institutes of Health: $599,414.00
  • National Institutes of Health: $588,648.00
  • National Institutes of Health: $609,680.00

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Technology
T-Lymphocytes
Transplants
Graft vs Host Disease
Opportunistic Infections
Transplantation
Tissue Donors
Histocompatibility
Mycoses
Cell Transplantation
Virus Diseases
Hematologic Neoplasms
Cell- and Tissue-Based Therapy
Stem Cells
Clinical Trials
Antigens
Survival
Mortality

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)