Cell and Gene Therapy Program
(Malcolm K. Brenner, M.D., Ph.D., Leader;
Helen Heslop, M.D., Co-Leader)
This program involves 24 investigators, approximately 18 of whom have independent third-party findings, and who conduct basic, translational, and clinical research organized among four major themes.
Stem Cell transplantation
Investigators in this area focus on approaches to improve the outcome of allogeneic SCT for malignant disease by developing safer preparative regimens and by devising approaches to enhance immune reconstitution following the procedure. Based on animal and human pre-clinical data, NCI-funded clinical trials have emerged from these studies that utilize CD45 monoclonal antibodies as a minimally toxic sub-ablative preparative regimen for allo-SCT and that prepare donor T lymphocytes depleted of alloreactive cells to enhance immune recovery after mismatched allogeneic SCT.
Adoptive immunotherapy with cytotoxic T lymphocytes directed to viral antigens
This approach is used to treat viral associated malignancies, particularly those associated with Epstein-Barr virus. In a series of NIH-supported pre-clinical and clinical studies, we have used genetically modified CTL to treat immunoblastic lymphoma, Hodgkin Disease and Nasopharyngeal carcinoma. The approach is now being extended to malignancies associated with papilloma virus and with SV40 and to the treatment of stem cell transplant recipients with adenovirus and cytomegalovirus specific CTL.
Active immunotherapy with genetically modified tumor cells
This approach has been successfully used in NIH funded studies for patients with pediatric and adult hematologic malignancies including B-Chronic lymphocytic leukemia. The combination of IL2, Lymphotactin and or CD40L gene transfer into tumor cells has been shown to induce Th1 and cytotoxic T cell anti-tumor immune responses and tumor regression. Single chain variable region antibodies have been isolated from the B cells of responding patients and are now being investigated as effector molecules.
Use of Adenoviral Vectors encoding lytic genes
Based on our earlier experience with administration of adenoviral vectors encoding the Thymidine kinase gene to patients with prostate cancer, we have extended the approach to include additional treatment modalities (radiation/chemotherapy), additional transgenes intended to enhance the anti-tumor immune response (IL12) and additional tumor targets (retinoblastoma).
These activities are supported by two manufacturing laboratories which prepare gene transfer vectors and purified and modified cells made to meet current Good Manufacturing or Good Tissue Practice guidelines. Each of these laboratories is one of three selected in each category to be National Centers to supply vectors and cells to other NIH investigators.Investigators
- Malcolm Brenner, Ph.D., M.B.B.Ch.
- Helen Heslop, M.D., M.B., Ch.B.
- Cliona Rooney, Ph.D.
- Robert Krance, M.D.
- Adrian Gee, Ph.D.
- Ron Fu Wang
- Si Yi Chen
- Jason Shohet, M.D., Ph.D.
- Timothy Thompson, Ph.D.
- Alan Davis, Ph.D.
- Betsy Davis, Ph.D.
- Sean Zhang, M.D., Ph.D.
- Nancy Templeton Smyth, Ph.D.
- Richard Hurwitz, M.D.
- Joanne Hurwitz
- Uday Popat, M.D., B.S.
- George Carrum, M.D.
- Catherine Bollard, B.S., M.B.B.S.
- Steven Gottschalk, M.D.
- Ingrid Kuehnle, M.D.
- Elio Vanin, Ph.D.
- Heidi Russell, M.D., B.S.
- Brian Butler, M.D.
- Richard Sutton, M.D., Ph.D.