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.
|Effective start/end date||5/1/04 → 4/30/10|
- 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
- Immunology and Microbiology(all)