Seminarium - T cells as a drug for the immunotherapy of cancer
T cells as a drug for the immunotherapy of cancer"
Professor Dr. Steven A. Rosenberg, M.D. PhD
Chief of the NIH Surgery Branch, Senior Investigator and Head, Tumor Immunology Section, Washington, DC, USA and Foreign Adjunct Professor in Cell Therapy, Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
We would be delighted if you would be able to join Dr. Rosenberg for a dinner-mingle reception from 5-6.30 at Nobel Forum.
For any questions, please contact Rose at Rose.Wang@ki.se phone: 0700458072
Matti Sällberg, Ernest Dodoo and Mark Maeurer
Dr. Rosenberg’s key achievements:
Discovery that IL-2 administration could mediate durable (and likely curative) cancer regressions in patients with metastatic melanoma and kidney cancer. Many of these patients remain cancer-free over 25 years after treatment. Dr. Rosenberg’s studies led to the first approval of an immunotherapy for human cancer by the US Food and Drug Administration. (N. Engl. J. Med. 313:1485-1492, 1985; J. Am. Med. Assoc. 256:3117-3124, 1986; N. Engl. J. Med. 316:889-897, 1987).
Discovery that the administration of anti-tumor T lymphocytes (TIL) could mediate the regression of established metastatic melanoma in humans (N. Engl. J. Med. 319:1676-1680, 1988; J. Natl. Cancer Inst. 86: 1159-1166, 1994). This paper directly demonstrated that T lymphocytes were the direct effectors of cancer regression in humans and opened the field of the cell therapy of cancer. Dr. Rosenberg then discovered that lymphodepletion prior to adoptive transfer of ant-tumor T cells (TIL) could markedly improve the clinical effectiveness of cell transfer immunotherapy (Science 298:850-854, 2002) that ultimately led to durable complete regressions of metastatic melanoma in up to 25% of patients (Clin. Cancer Res. 17:4550-4557, 2011).
First ever insertion of foreign genes into humans. This work used anti-tumor T lymphocytes genetically engineered to express a marker gene (neomycin phosphotransferase) to track the distribution of T-cells after infusion to patients and opened the door to the field of human gene therapy (N. Engl. J. Med. 323:570-578, 1990).
Dr. Rosenberg was the first to demonstrate in humans that blockade of the checkpoint inhibitor, CTLA4, could mediate the regression of metastatic melanoma in patients (Proc. Natl. Acad. Sci. 100:8372-8377, 2003). Subsequent multiinstitutional studies by others led to the approval of an anti-CTLA4 monoclonal antibody (ipilimumab) as immunotherapy for patients with metastatic melanoma by the FDA in 2011.
First demonstration of the successful gene therapy of any cancer in humans using genetically engineered lymphocytes encoding an anti-tumor T-cell receptor (targeting the MART-1 melanoma antigen) (Science 314:126-129, 2006; Blood 114:535-546, 2009). These studies opened the field of the gene therapy of cancer. Dr. Rosenberg was the first to discover successful gene therapy of a non-melanoma solid cancer in humans using genetically engineered lymphocytes encoding an anti-tumor T-cell receptor targeting the NY-ESO-1 cancer-germline antigen in patients with sarcomas (J. Clin. Oncol. 29:917-924, 2011).
First demonstration of the successful gene therapy in humans using a a chimeric antigen receptor (CAR) (targeting CD19) that could successfully mediate complete regression in patients with B-cell lymphomas and leukemias refractory to other treatments (Blood 116:3875-3886, 2010; Blood 119:2709-2720, 2012)
Discovery that anti-tumor T cells targeting unique somatic immunogenic cancer mutations could lead to the regression of a common human epithelial cancer (Science 344:641-645, 2014). This approach provided a blueprint for the immunotherapy of common cancers now being pursued around the world.