Development of Augmented Leukemia/Lymphoma-Specific T-Cell Immunotherapy for Deployment with Haploidentical, Hematompoietic Progenitor-Cell Transplant
Annual rept. 15 Apr 2007-14 Apr 2008
M D ANDERSON CANCER CENTER HOUSTON TX
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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.
- Medicine and Medical Research