Malcolm K. Brenner, MD, PhD

Professor Departments of Pediatrics and of Medicine Section of Hematology-Oncology, Baylor College of Medicine

Director Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital

Contact Information:
mbrenner@bcm.edu
832-824-4671

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Education:
B.A., Cambridge University, England
MB, B Chir, Cambridge University, London, England
Ph.D., Cambridge University, England
FRCPath, FRCP

Research Interests:
Dr. Brenner's research in tumor immunology has shown that tumor cells genetically modified to express immunostimulatory genes will induce effective antitumor responses in a range of syngeneic animal models.  He has compared the relative immunostimulatory and antitumor potencies of autologous and allogeneic tumor vaccines in children with advanced neuroblastoma, obtaining evidence of local immunity with both types of vaccines, with the autologous vaccine showing more potent systemic activity. In follow-up studies, efforts are being made to increase the immunogenicity of the tumor cells by transducing them with a combination of lymphotactin, a T- lymphocyte chemotaxin, and IL2, to amplify the response of tumor specific T cells attracted to the site of tumor inoculation. This strategy has proved to be extremely effective in several different murine models, and having shown promise in patients with relapsed tumor, it is now being extended to individuals with minimal residual disease. Similar studies are underway in patients with acute leukemia. Dr Brenner's laboratory is also using molecular techniques to define the antigens on tumors recognized by stimulated immune system cells, with the aim of genetically modifying cells, so that they specifically recognize such antigens. Another area of research aims to improve immune reconstitution. Cancer patients who receive T-cell-depleted hematopoietic stem cell (HSC) transplants to prevent GVHD remain at risk for viral infections and relapse. An alternative strategy to reconstitute antigen-specific responses to multiple viruses and tumor cells would be to selectively deplete the graft of alloreactive cells that initiate GVHD, thus preserving tumor- and virus-specific cells. To test this hypothesis, Dr. Brenner and colleagues have developed techniques for depleting alloreactive T cells and transferring them to HSC recipients to provide antiviral and antitumor activity without the risk of GVHD. Trainees in this laboratory have the opportunity to undertake translational research in the field of tumor immunology and interact strongly with the vector and GMP cores and the Regulatory Affairs Office.

Selected Original Articles 2006-2007:
Rousseau RF, Biagi E, Dutour A, Yvon ES, Brown MP, Lin T, Zhuyong M, Grilley B, Popek E, Heslop HE, Gee AP, Krance RA, Popat U, Carrum G, Margolin JF, Brenner MK.  Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L an IL-2 after chemotherapy and allogeneic stem cell transplantation.   Blood. 2006; 107(4):1332-41.

Russell HV, Brenner MK, et al.  Phase I trial of vaccination with autologous neuroblastoma tumor cells genetically modified to secrete IL-2 and lymphotactin.  Journal of Immunotherapy. 2006, In Press.

Rossig C, Bar A, Pscherer S, Altvater B, Pule M, Rooney CM, Brenner MK, Jurgens H, Vormoor J.  Target antigen expression on a professional antigen-presenting cell induces superior proliferative antitumor T-cell responses via chimeric T-cell receptors.  J Immunother. 2006 Jan-Feb; 29(1):21-31.

Lacuesta K, Buza E, Hauser H, Granville L, Pule P, Corboy G, Finegold M, Weiss H, Chen SY, Brenner MK, Heslop HE, Rooney CM, Bollard CM.  Assessing the safety of cytotoxic T lymphocytes transduced with a dominant negative transforming growth factor-β receptor.  J Immunother 2006 May-June; 29(3):250-260.

Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A, Yvon E, Weiss H, Cobbold M, Gaspar HB, Rooney C, Kuehnle I, Ghetie V, Schindler J, Krance R, Heslop HE, Veys P, Vitetta, Brenner MK.  Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation.  Blood. 2006 Sept 15;108(6):1797-1808.

Loskog A, Giandomenico V, Rossig C, Pule M, Dotti G, Brenner MK.  Addition of the CD28 signaling domain to chimeric T cell receptors enhances chimeric T cell resistance to T regulatory cells.  2006.  Leukemia.  2006 Oct; 20 (10):1819-28.

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 clinical relevant effects in immunocompromised patients.  2006.  Nat Med. 2006 Oct; 12(10):1160-6.

Vera J, Savoldo B, Vigouroux S, Biagi E, Pule M, Rossig C, Wu J, Heslop HH, Rooney CM, Brenner MK and Dotti G.  T-lymphocytes redirected against the kappa light chain of human immunoglobulins efficiently kill mature B-lymphocyte derived malignant cells.  Blood 2006 Dec 1;108(12):3890-7.

Savoldo B, Gossal A, Hammer NM, Zhang L, Lopez T, Gee AP, Lin YF, Quiros-Tejeira RE, Reinke P, Schnert S, Gottschalk S, Finegold MJ, Brenner MK, Rooney CM, Heslop HE.  Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTL).  Blood. 2006 Nov 1;108(9):2942-9.

Book Chapters:
Pule M, Brenner MK. Gene transfer: methods and applications. In: Childhood Leukemia, 2nd ed. Ching-Hon Pui.  Cambridge University Press, pp. 661-678, 2006.

Review Articles:
Tey SK, Brenner MK.  The continuing contribution of gene marking to cell and gene therapy.  Mol Ther. 2007 Apr;15(4):666-76.

©2002, Cell And Gene Therapy, Baylor College of Medicine
One Baylor Plaza, N1002, Houston, TX 77030, (713)798-1246
URL: http://www.bcm.edu/genetherapy Email:cagt@bcm.edu
(Modified:August 15, 2006- SM)