Dr. Topalian’s basic studies of human anti-tumor immunity response have provided a framework for developing immunotherapies for melanoma and other cancers, including cancer vaccines, adoptive T cell transfer, and immune-modulating monoclonal antibodies. Her early work established that cytolytic “killer” T lymphocytes in melanoma patients could specifically recognize cancer cells from the same patient. Later studies confirmed the existence of “shared” melanoma antigens (proteins) across tumors from different patients, paving the way for the development of melanoma vaccines. Her seminal investigations into the role of CD4+ T “helper” cells in human anti-tumor immunity revealed the existence of tumor-specific CD4+ T cells in patients with melanoma and other cancers. Dr. Topalian’s current research focuses on manipulating “immune checkpoints” such as PD-1 in cancer therapy, discovering biomarkers predicting response and resistance to anti-PD-1 therapy, and developing new strategies such as neoadjuvant (pre-surgical) anti-PD-1 administration and effective treatment combinations.
Clinical Trial Keywords
Anti-PD-1; anti-PD-L1; Immunotherapy; Biomarker; Neoadjuvant.
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Brahmer JR, Drake CG, Wollner I, Powderly J, Picus J, Sharfman W, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, and Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics and immunologic correlates. J Clin Oncol 2010; 28:3167-75
Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, Chen L. Co-localization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Science Transl Med 2012; 4:127ra37
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443-54
Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker A, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Moreno BH, Sharon E, Cheever MA, Topalian SL. Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy. J Clin Oncol 2019; 37:693-702
Topalian SL, Taube JM, Pardoll DM. Neoadjuvant checkpoint blockade for cancer immunotherapy. Science 367, eaax0182 (2020). DOI: 10.1126/science.aax0182