Medicine, Hematology/Oncology Director, Center for Cell and Gene Therapy
Dr. Malcolm Brenner has developed a method that not only targets the killing power of immune system T-cells against specific antigens or proteins found on tumors, but also insures that the levels of these T-cells remain high long enough to be effective. To do this, in a series of elegant experiments, he has combined the specially developed T-cells with CARs chimeric antigen receptors that bind to specific proteins on tumors cells and trigger the killing potential of the T-cells. In a recent experiment, he and his colleagues extended the life of this construct by adding a special stimulatory molecule that increases the numbers of T-cells and their tumor-fighting potential. His methodology has the promise not only to kill tumors cell but also will translate well into actual treatment in the clinic.
Dr. Brenner's nomination was based on the following publications:
Pule,M.A., Savoldo,B., Myers,G.D., Rossig,C., Russell,H.V., Dotti,G., Huls,M.H., Liu,E., Gee,A.P., Mei,Z., Yvon,E., Weiss,H.L., Liu,H., Rooney,C.M., Heslop,H.E., & Brenner,M.K. (2008) Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nature Medicine, 14, 1264-70.
Yvon,E., Del,V.M., Savoldo,B., Hoyos,V., Dutour,A., Anichini,A., Dotti,G., & Brenner,M.K. (2009) Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cells. Clin Cancer Res, 15, 5852-60.
Savoldo,B., Ramos,C.A, Liu,E,. Mims,M., Keating,M., Carrum,G.,Kamble,R., Bollard,C., Gee,A., Mei,Z., Liu,H., Grilley,B., Rooney,C.M., Heslop,H.E., Brenner,M.K., Dotti,G. (2011) CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. Journal of Clinical Investigation,121(5), 1822-6.