| Experimental Therapeutics Faculty |
Aaron Rapoport, M.D. |
Research Interests/Projects:
Identification of differentially regulated genes in Burkitt’s lymphoma cells vs. normal B cells. In this project, we have used mRNA differential display technology to identify nearly 20 genes, some known and some unknown, that appear to be differentially regulated between a Burkitt’s lymphoma cell line and normal tonsillar B cells. At least four genes have been shown to be expressed more than 20-fold higher in the Burkitt’s cells by Northern blot analysis. One of the genes identified by this method is apparently new, and we are currently attempting to obtain a full length cDNA for this gene.
Auto-transplantation for CML using ex-vivo expanded autologous T-cells. Autologous stem cell transplants have been performed for patients with CML who lack histocompatible donors. However, disease eradication is rare with this therapy due to the apparent absence of leukemia-reactive autologous T-cells. Evidence suggests that such cells do exist but in a state of anergy due to presentation of leukemic antigens without critical “costimulatory” signals. The research hypothesis is that ex-vivo expansion and activation of autologous T-cells using “costimulation” with anti-CD3/anti-CD28-conjugated magnetic beads will restore anti-leukemic cell recognition and cytolytic function. Infusion of treated cells to patients with minimal disease after auto-transplantation may induce complete cytogenetic and molecular remissions. Two patients treated on this protocol have had major cytogenetic responses at 2+ and 6+ months of follow-up. Correlative laboratory studies designed to assay for development of anti-leukemic immunity in these patients are underway. Support for this work has been obtained from an American Cancer Society (ACS) institutional award and the Immunex Corp.
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