Malcolm K. Brenner, M.D., Ph.D.
Departments of Pediatrics and of Medicine
Section of Hematology-Oncology, Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, The Methodist Hospital
Shell Center for Gene Therapy, Baylor College of Medicine
B.A., Cambridge University, England
MB, B Chir, Cambridge University, London, England
Ph.D., Cambridge University, England
One interest of Dr. Brenner's research is in the field of tumor immunology. Tumor cells that have been genetically modified to express immunostimulatory genes will induce effective anti-tumor responses in a range of syngeneic animal models. Dr. Brenner has compared the relative immunostimulatory and anti tumor potency of autologous and allogeneic tumor vaccines in children with advanced neuroblastoma and in adult with acute and chronic leukemia. Recipients of both autologous and allogeneic vaccines showed evidence of local immunity but the autologous vaccine showed more potent systemic activity. In follow up studies, the immunogenicity of the tumor cells was increased 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 approach has been extended to individuals with minimal residual disease. Similar studies are also underway in patients with acute and chronic leukemia. Dr Brenner's laboratory is also using molecular techniques to increase the effectiveness of cytotoxic T cell killing of tumor cells.
Dr Brenner is Associate Editor of Blood and of Molecular Therapy and the Principal Investigator or Co-investigator on 5 NIH grants.
Selected Recent Publications
Shohet JM, Hicks MJ, Plon SE, Burlingame SM, Stuart S, Chen SY, Brenner MK, Nuchtern JG. Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. Cancer Research (in press).
Rossig C, Bollard CM, Nuchtern JG, Rooney CM, Brenner MK. Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T cell receptors: potential for improved immunotherapy. Blood 99:2009-2016, 2002.
Savoldo B, Cubbage ML, Durett AG, Goss J, Huls MH, Liu Z, Lopez T, Gee AP, Ling PD, Brenner MK, Heslop HE, Rooney CM. Generation of Epstein-Barr virus 9EBV-specific CD4+ cytotoxic T cells (CTL) from virus naive individuals. J Immunology, 168:909-918, 2002.
Bollard CM, Rossig C, Calonge MMJ, Huls MH, Wagner HJ, Massague J, Brenner MK, Heslop HE, Rooney CM. Adapting a TGF-_-related tumor protection strategy to enhance anti-tumor immunity. Blood, 99:3179-3187, 2002.
Yotnda P, Chen D-H, Chiu w, Piedra PA, Davis A, Smyth Templeton N, Brenner MK, Huls MH, Wagner HJ, Massague J, Brenner MK, Heslop HE, Rooney CM. Adapting a TGF-__related tumor protection strategy to enhance anti-tumor immunity. Blood, 99:3179-3187, 2002.
Yotnda P, Chen D-H, Chiu w, Piedra PA, Davis A, Smyth Templeton N, Brenner MK. Bilamellar cationic liposomes protect adenovectors from pre-existing humoral immune responses. Molecular Therapy, 5:233-241, 2002.
Dotti G, Savoldo B, Yotnda P, Rill D, Brenner M. Transgenic expression of CD40-Ligand (CD40L) produces an in vivo antitumor immune response against both CD40 positive and negative plasmacytoma cells. Blood, 100:200-207, 2002.
Krance RA, Kuehnle I, Rill DR, Mei Z, Pinetta C, Evans W, Brown MP, Pule M, Heslop HE, Brenner MK. Hematopoietic and Immunomodulatory effects of lytic CD45 monoclonal antibodies in patients with hematologic malignancies. Biology of Blood and Marrow Transplantation. Biol Blood Marrow Transplant 4:273-281, 2003.
Biagi E, Yvon E, Dotti G, Amrolia PJ, Takahashi S, Popat U, Marini F, Andreeff M, Brenner MK, Rousseau RF. Bystander transfer of functional human CD40 ligand from gene-modified fibroblasts to B-chronic lymphocytic leukemia cells. Human Gene Therapy 14:545-559, 2003.
Savoldo B, Huls MH, Liu Z, Volk, H-D, Reinke P, Sabat R, Babel N, Jones JF, Webster-Cyriaque J, Gee AP, Brenner MK, Heslop HE, Rooney CM. Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection. Blood (in press).
Rousseau RF, Haight AE, Hirschmann-Jax C, Yvon E, Rill DR, Mei Z, Smith SC, Inman S, Cooper K, Alcoser P, Popek E, Davidoff A, Bowman LC, Brenner MK, Strother D. Local and systemic effects of an allogeneic tumor cell vaccine combining transgenic human lymphotactin with Interleukin-2 in patients with advanced or refractory neuroblastoma. Blood (in Press).
Wulf GG, Luo KL, Goodell MA, Brenner MK, Anti-CD45 mediated cytoreduction to facilitate Allogeneic Stem Cell Transplantation. Blood: (in Press).