Bruce Levine, Ph.D. University of Texas MD Anderson Cancer Center

TRANSPLANTATION/IMMUNE RECONSTITUTION

Trial of immune reconstitution with CD3/CD28 bead activated T-cells following chemo-immunotherapy in patients with chronic lymphocytic leukemia

Grant awarded in 2009

Abstract:

Our project is based on the hypothesis that infusing patients with activated T-cells will influence quantitative and functional immune reconstitution in CLL patients following chemotherapy. This should result in reduced rate of infectious complications and may even delay the time to disease progression.

We are conducting a multi-center trial in conjunction with Drs. Chitra Hosing and EJ Shpall of MD Anderson Cancer Center and Dr. Stephen Schuster and Dr. Carl June at University of Pennsylvania.

The premise of the trial is to evaluate the efficacy of administering CD3/CD28 activated T-cells to CLL patients following treatment with fludarabine or alemtuzumab-based chemo-immunotherapy.

CD3 and CD28 are proteins found on T-cells that do not function properly in CLL patients. We are applying microbeads to CLL patients' T-cells which contain antibodies that attach to CD3 and CD28 on T-cells to activate and expand them. By activating the T-cells, the microbeads turn on the anti-cancer and anti-infection activity and allow T-cells to multiply at an accelerated rate. Properly functioning CD3 and C28 on T-cells allows the immune system to better fight infection and cancer.

Patients enrolled in the trial will undergo apheresis to collect T-cells which will then be co-cultured with CD3/CD28 microbeads. Those subjects who achieve a complete or partial response to the chemo-immunotherapy based regimen will receive an infusion of their activated T-cells. Prior to, and multiple times after T-cell infusion, blood draws will be performed to assess immune reconstitution and immune function as compared to baseline.