This study will determine the feasibility of using autologous activated T cells for the treatment of B-CLL. Xcyte s technology uses para-magnetic beads covalently coated with anti-CD3 and anti-CD28 anti-bodies, which makes the bead a potent polyclonal activator of T cells. Cells generated this way have been used at the University of Chicago to treat relapsed/chemorefractory B Cell-NHL patients. This trial represents the first successful use of an ex-vivo costimulatory autologous T cell immunotherapeutic approach for patients with this malignancy. B-CLL patients present special difficulties for this therapy, including high leukemic burden in the blood, associated with T cell immunosuppression and hypo- gammaglobulinemia. The proposed study is designed to address using Xcyte s technology in a clinical trial for B-CLL patients who have failed primary therapy. The study will assess the ability of coordinated CD3xCD28 activation to expand T cells from the peripheral blood of B-CLL patients to therapeutically relevant numbers, and to correct T cell defects which prevent them from responding to autologous leukemia cells. Successful demonstration of these aims will justify the initiation of a phase I clinical trial in B-CLL conducted jointly by Xcyte Therapies and collaborators at the Oregon Health Sciences University.

Proposed Commercial Applications

Xcyte Therapies has built a GMP manufacturing facility to generate activated T cells for clinical trials. A pivotal trial for 3x28 activated T cells will begin in 2000. About 20,000 NHL patients will be eligible for this therapy in the USA, and another 20,000 patients with other malignancies, such as B-CLL will also be eligible. The therapy may have applications to breast, lung and prostate cancer as well.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43CA083473-01
Application #
6016572
Study Section
Special Emphasis Panel (ZRG1-SSS-4 (02))
Program Officer
Muszynski, Karen
Project Start
1999-09-24
Project End
2000-12-31
Budget Start
1999-09-24
Budget End
2000-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Xcyte Therapies, Inc.
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98134
Bonyhadi, Mark; Frohlich, Mark; Rasmussen, Angela et al. (2005) In vitro engagement of CD3 and CD28 corrects T cell defects in chronic lymphocytic leukemia. J Immunol 174:2366-75