Method for Expanding Allodepleted Antigen Specific T Cells
Description of Invention:
Available for licensing and commercial development are methods of producing a population of purified non-alloreactive antigen-specific T cells that recognize an antigen of interest. Thus, the population of donor T cells can be used to produce immune response against the antigen of interest (e.g., cytomegalovirus) in a recipient without producing an immune response to the recipient. Currently available methods for isolating and expanding antigen-specific T cells can be inefficient and produce populations of cells that include donor-reactive T cells. The present method enables rapid production of populations of T cells that recognize an antigen of interest but are depleted for alloreactive T cells: A population of donor T cells is contacted with a population of irradiated recipient antigen presenting cells (T-APCs) to produce a population of alloreactive donor T cells. The alloreactive T cells are removed by purification with an antibody that specifically binds a cell surface marker (e.g., CD25, CD69, CD38 or CD71). The population of allo-depleted donor cells is then contacted with donor T antigen presenting cells (T-APCs) expressing an antigen of interest and produces a population of donor allo-depleted activated CD4 and CD8 T cells.
Application:
Immune response to opportunistic infections in immuno-compromised transplant or graft recipients
Market:
Cytomegalovirus
General post-transplant opportunistic infections
Inventors:
J. Joseph Melenhorst (NHLBI) A. John Barrett (NHLBI)
Patent Status:
DHHS Reference No. E-136-2006/0
Relevant Publication:
JJ Melenhorst, TH Brummendorf, M Kirby, PM Lansdorp, AJ Barrett. CD8+ T cells in large granular lymphocyte leukemia are not defective in activation- and replication-related apoptosis. Leuk Res. 2001 Aug;25(8):699-708. [PubMed abs]
H Fujiwara, JJ Melenhorst, F El Ouriaghli, et al. In vitro induction of myeloid leukemia-specific CD4 and CD8 T cells by CD40 ligand-activated B cells gene modified to express primary granule proteins. Clin Cancer Res. 2005 Jun 15;11(12):4495-4503. [PubMed abs]
SR Solomon, S Mielke, BN Savani, A Montero, L Wisch, R Childs, N Hensel, J Schindler, V Ghetie, SF Leitman, T Mai, CS CarterS, R Kurlander, EJ Read, ES Vitetta, AJ Barrett. Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood. 2005 Aug 1;106(3):1123-1129. [PubMed abs]
JJ Melenhorst, SR Solomon, A Shenoy, NF Hensel, JP McCoy Jr, K Keyvanfar, AJ Barrett. Robust expansion of viral antigen-specific CD4+ and CD8+ T cells for adoptive T cell therapy using gene-modified activated T cells as antigen presenting cells. J Immunother. 2006 Jul-Aug;29(4):436-443; discussion 365-366. [PubMed abs]
Licensing Status: This technology is no longer available for licensing.
For Additional Information Please Contact: Michael Shmilovich J.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5019
Email: shmilovm@mail.nih.gov
Fax: (301) 402-0220
