Email

mbrenner@bcm.edu

Positions

Professor

Center for Cell and Gene Therapy
Baylor College of Medicine
Houston, TX US

Professor

Molecular and Human Genetics
Baylor College of Medicine

Professor

Pediatrics
Baylor College of Medicine

Professor

Medicine
Baylor College of Medicine

Professor

Program in Translational Biology & Molecular Medicine
Baylor College of Medicine

Fayez Sarofim Chair

Baylor College of Medicine
Houston, Texas United States

Member

Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States

Addresses

Houston Methodist Hospital (Clinic)

Blood, Marrow and Cell Therapy Center
6565 Fannin Ste 800
Houston, TX 77030
United States
Phone: (713) 441-1450

Education

BA from University Of Cambridge

01/1972 - Cambridge, United Kingdom

MBChB from Westminster Medical College

01/1975 - London, United Kingdom

PhD from University Of Cambridge

01/1981 - Cambridge, United Kingdom

Professional Interests

• Use of gene therapy to improve responses to cancer

Professional Statement

Dr. 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.

Websites

Selected Publications

• Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, Straathof K, Liu E, Durett AG, Grilley B, Liu H, Cruz CR, Savoldo B, Gee AP, Schindler J, Krance RA, Heslop HE, Spencer DM, Rooney CM, Brenner MK "Inducible apoptosis as a safety switch for adoptive cell therapy.." N. Engl. J. Med.. 2011 Nov 3;365(18):1673-83. Pubmed PMID: 22047558
• Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, Bollard CM, Liu H, Wu MF, Rochester RJ, Amrolia PJ, Hurwitz JL, Brenner MK, Rooney CM "Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients.." Blood. 2010 Feb 4;115(5):925-35. Pubmed PMID: 19880495
• Pule MA, Savoldo B, Myers GD, Rossig C, Russell HV, Dotti G, Huls MH, Liu E, Gee AP, Mei Z, Yvon E, Weiss HL, Liu H, Rooney CM, Heslop HE, Brenner MK "Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma.." Nat. Med.. 2008 Nov;14(11):1264-70. Pubmed PMID: 18978797
• Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS, Carrum G, Krance RA, Chang CC, Molldrem JJ, Gee AP, Brenner MK, Heslop HE, Rooney CM, Bollard CM "Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.." Nat. Med.. 2006 Oct;12(10):1160-6. Pubmed PMID: 16998485