Chitra Hosing, M.D., Elizabeth Shpall, M.D., John Gribben, M.D., DSc University of Texas MD Anderson Cancer Center, Barts Cancer Center of Excellence/ The London School of Medicine (United Kingdom)

TRANSPLANTATION/IMMUNE RECONSTITUTION

Activating immune cells in CLL

Update:

Aim: Test the hypothesis that infusion of activated T-cells will influence immune reconstitution in patients receiving chemo-immunotherapy for CLL:

CLL in itself can cause disease related immunosuppression that is compounded by the immunosuppression induced by agents that are commonly used in the treatment of this disease. T-cells activated using CD3xCD28 microbeads may reverse some of these immune defects. In this study, we plan to give activated T-cell infusion to patients with CLL following treatment with fludarabine or alemtuzumab-based chemo-immunotherapy. A total of 8 patients have been enrolled in a multi-center clinical trial which will help us to determine the feasibility and safety of the infusion of autologous CD3 xCD28 bead-activated T-cells. The trial is a collaboration between Alliance members here at MD Anderson and at University of Pennsylvania, including Bruce Levine, Carl June, and Stephen Schuster.

Aim: Evaluate infusion of expanded umbilical cord blood (CB) T-cells following cord blood transplantation:

CB T-cells are an attractive source for adoptive immunotherapy and cellular therapy, but adult recipients of CB transplants often experience delays in hematological and immunologic reconstitution that increase the risk of infection. We propose to expand CB T-cells, using CD3xCD28 microbeads, to sufficient numbers which could contribute to the reconstitution of immunity and enhance anti-tumor activity. When incubated with peripheral blood T-cells, these microbeads can stimulate marked proliferation of antigen-specific T-cells. Validations for CB T-cell expansion are in progress.

Through our laboratory studies during the course of this grant, we were able to show that generating CLL-specific effectors from partially HLA-matched CB lymphocytes is feasible and practical. Further, we were able to demonstrate functional cytotoxic activity against untreated CLL cells, a distinct technological advancement in comparison to previous cell therapies that have sought to generate CLL-specific responses. These preclinical results support further exploration of this technique as a promising treatment modality in conjunction with CB transplantation.