Malcolm K. Brenner, MD, PhD
Department or Service
- Texas Medical Center
Phone: (832) 824-4671
- Cell and gene therapy
- Bone Marrow Transplant / Stem Cell Transplant
- Brain tumors
Professor, Department of Pediatrics, Section of Hematology/Oncology, Baylor College of Medicine
Professor, Department of Molecular and Human Genetics, Baylor College of Medicine
Professor, Department of Medicine, Baylor College of Medicine
Professor, Program in Translational Biology & Molecular Medicine, Baylor College of Medicine
Fayez Sarofim Chair, Baylor College of Medicine
Member, Executive Committee, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine
|Royal Brompton Hospital, London||fellowship||Hematology-Oncology||1997|
|University Of Cambridge||PhD||Doctor of Philosophy||1981|
|University of Chicago, Pritzker School of Medicine||fellowship||Immunology||1981|
|Chelsea & Westminster Hospital||fellowship||Medical Registrar||1978|
|Chelsea & Westminster Hospital||internship||Surgery||1976|
|Charing Cross & Westminster Medical School||medical school||Doctor of Medicine||1975|
|University Of Cambridge||bachelors||Bachelor of Arts||1972|
Dr. Malcolm Brenner is Director of the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children's Hospital, and Houston Methodist Hospital, which is responsible for the stem cell transplant programs at these institutions. Dr. Malcolm Brenner's clinical interests span many aspects of stem cell transplantation, using genetic manipulation of cultured cells to obtain therapeutic effects.
Clinical Special Interests
Cell and Gene Therapy
Bone Marrow Transplantation
|British Society for Hematology||Member|
|British Society for Immunology||Member|
|International Society for Hematology and Graft Engineering||President|
Dr. Malcolm Brenner's primary research interest is the use of gene transfer to augment the immune response to human tumors, using vaccines and adoptive transfer of genetically modified T cells.
In neuroblastoma, Dr. Brenner and co-investigators have shown that T cells expressing a chimeric antigen receptor (CAR) for a surface marker (GD2) on neuroblastoma cells can produce tumor responses in more than half the patients with refractory or relapsed disease leading to complete remission in 3/11 patients. His Center is also studying the benefits of T cells modified with CARs directed to other tumor antigens on hematological malignancies and solid tumors including Hodgkin Disease and Glioblastoma multiforme and initial clinical results are promising. Efforts are being made to further increase the effectiveness of these CAR-T cells by incorporating genes that enhance T cell growth and survival and that render the T cells resistant to the inhibitory effects of many human tumors.
To enhance the safety of genetically modified T cells, Dr. Brenner and colleagues have implemented an inducible caspase system that will rapidly cause apoptosis of T cells within minutes of administration of a small molecule dimerizing drug, allowing adverse effects from the T cells to be reversed. Initial clinical trials showed significant activity, and the approach is now being broadened to other novel T cell therapeutics.
Dr. Brenner’s group combines these adoptive transfer strategies with immunization against the tumors to produce synergistic benefits and clinical studies in chronic lymphocytic leukemia have recently begun.
Finally, in collaboration with the laboratories of Drs. Rooney, Heslop and Bollard, Dr. Brenner is continuing to study the use of gene modified cytotoxic T lymphocytes to prevent and treat the Epstein Barr virus associated malignancies, immunoblastic lymphoma, Hodgkin disease, and nasopharyngeal cancer (NPC). By transducing dendritic cells with EBV antigens, we are able to generate potent immune responses against the weak EBV latency antigens expressed in Hodgkin disease and NPC. Studies in 23 patients with relapsed or refractory EBV-positive Hodgkin and Non-Hodgkin lymphoma patients have produced complete responses in more than half. The potential to increase the effectiveness of the T-cells in vivo using monoclonal antibodies directed to immunological checkpoints is now being evaluated in clinical trials.