Description of Invention:
Allogeneic stem cell transplantation represents a potentially curative treatment option for patients with both hematologic and solid cancers, and for patients with other non-malignant conditions. However, the clinical application of allogeneic stem cell transplantation is limited by T cell immune reactions.
The current invention embodies a method for enrichment of donor T cells of Tc1 and Tc2 phenotypes by in vitro culture. This method represents a significant advance in terms of T cell numbers produced, level of cytokine polarization, and efficacy of in vivo effects. In murine transplantation models, this method greatly reduces graft-versus-host disease (GVHD) associated with donor CD8 cell administration. Murine Tc2 cells generated by this method are particularly potent in abrogating graft rejection by a mechanism that does not involve GVHD. In addition, this method can generate Tc1 and Tc2 cells that mediate graft-versus-tumor (GVT) effects against murine breast cancer and murine leukemia. The Tc1 and Tc2 cells produced by this method are also amenable to insertion of a suicide gene, which represents a potential strategy for mediating potent allogeneic GVT effects, with subsequent reversal of T cell mediated GVHD. Allogeneic transplantation using Tc1 and Tc2 cells generated via this method may therefore represent an approach to increase the anti-tumor efficacy and reduce the GVHD-toxicity of allogeneic stem cell transplantation, and to extend allogeneic transplantation to those patients lacking an HLA-matched sibling.
Inventors:
D Fowler (NCI) U. Jung (NCI) J. Medin (NINDS) R. Gress (NCI) A. Erdmann (NCI) et al.
Patent Status:
DHHS Reference No. E-360-2001/0 --
U.S. Provisional Patent Application 60/336,473 filed 31 Oct 2001
PCT Application No. PCT/US02/35240 filed 31 Oct 2002, which published as WO 03/038062 on 08 May 2003
U.S. Patent Application No. 10/494,540 filed 29 Apr 2004
Portfolios: Internal Medicine Cancer
Cancer -Therapeutics-Immunomodulators and Immunostimulants Internal Medicine-Therapeutics-Anti-Inflammatory (including Autoimmune) Cancer -Therapeutics Internal Medicine-Therapeutics
For Additional Information Please Contact: Jennifer Wong
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4633
Email: wongje@mail.nih.gov
Fax: (301)402-0220
