Accession Number:

ADA488052

Title:

Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant

Descriptive Note:

Annual rept. 15 Apr 2007-14 Apr 2008

Corporate Author:

M D ANDERSON CANCER CENTER HOUSTON TX

Personal Author(s):

Report Date:

2008-05-01

Pagination or Media Count:

33.0

Abstract:

To develop T-cell therapies for B-cell malignancies we have developed a chimeric antigen receptor CAR which when expressed on the cell surface redirects T-cell specificity for CD19, a B-lineage cell-surface antigen. We have undertaken a series of systematic experiments to improve the ability of these CAR T cells to persist after adoptive transfer based on conditional expression of interleukin-2 IL-2 which is a potent cytokine that can prolong T-cell persistence. Firstly, we have combined T-cell therapy with antibody therapy directing both immunotherapies to B-cell antigens. To improve CD19-specific T-cell survival we combined a CD20-specific antibody with IL-2 which deposits IL-2 in the tumor microenvironment and is a surrogate for T-cell help TH. Secondly, we have developed a gene transfer platform to propagate CD19-specific CAR CD4 T cells that provide TH to CD8 T cells. Thirdly, we have re-engineered the CD19-specific CAR itself so that it can signal for endogenous production of IL-2 through chimeric CD28. These technologies will now be evaluated in animal models in preparation for deciding which to take forward to a clinical trial.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE