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Suzanne Louise Topalian, M.D.
Melanoma Program Director
Professor of Surgery
Languages: English, French
Expertise: General Surgery, Melanoma, Skin Cancer
Research Interests: Cancer immunology and immunotherapy
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Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Appointment Phone: 410-502-8218
401 N. Broadway
David H. Koch Cancer Research Building, Suite 508
Baltimore, MD 21231 map
Dr. Topalian received her undergraduate degree from Wellesley College and went on to receive her medical degree from Tufts University School of Medicine in 1979. She then went on to complete her residency in general surgery at the Thomas Jefferson University Hospital in Philadelphia, after which she held two fellowships — the first in Pediatric Surgery Research at the Children’s Hospital of Philadelphia (1982-1983), and the second in Surgical Oncology at the National Cancer Institute, NIH in Bethesda, Maryland (1985-1989). In 2006, after a 21-year tenure in the Surgery Branch of the National Cancer Institute, Dr. Topalian joined the Johns Hopkins faculty to lead the Melanoma Program in the Sidney Kimmel Comprehensive Cancer Center.
In the laboratory and in the clinic, Dr. Topalian serves as a physician-scientist whose research interests focus on cancer immunology and immunotherapy. She has published over 100 original research articles and reviews in this field and is internationally recognized for this work. Dr. Topalian’s basic studies of human anti-tumor immune responses have provided a foundation for the translational development of 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 tumor cells from the same patient. Later studies confirmed the existence of “shared” melanoma antigens (proteins) among tumors from different patients, paving the way for the clinical development of melanoma vaccines. Seminal investigations into the role of CD4+ T “helper” cells in human anti-tumor immune responses revealed the existence of tumor-specific CD4+ T cells in patients with melanoma and other cancers, and biochemical and molecular methods were devised for identifying the recognized tumor-associated proteins.
As the Director of the Melanoma Program, Dr. Topalian’s current work focuses on modulating immune checkpoints such as PD-1 in cancer therapy, and discovering biomarkers predicting clinical outcomes following treatment. She continues to work on devising optimal melanoma vaccines, based on biochemical and structural analyses, with the goal of exploring combination treatment regimens of vaccines with PD-1 blocking drugs. These pioneering efforts have opened new avenues of scientific interest and clinical investigation in cancer immunology, and have helped to establish immunotherapy as a treatment modality for cancer.
- Melanoma Program Director
- Professor of Surgery
- Professor of Oncology
- MD, Tufts University School of Medicine (1979)
- Jefferson Medical College of Thomas Jefferson University / General Surgery (1985)
- National Cancer Institute- NIH / Oncology (1989)
Research & Publications
Dr. Topalian's research prior to joining Hopkins revealed the existence of melanoma-associated proteins ("antigens") specifically recognized by human CD8+ killer and CD4+ helper T cells, paving the way for the clinical development of melanoma vaccines. Disappointing results with cancer vaccines in the clinic led to the realization that melanoma and many other human cancers can avoid immune detection and destruction by displaying molecular shields and secreting immune-suppressive factors. Dr. Topalian has led the clinical development of immune-modulating monoclonal antibodies to break through this shield and effectively treat patients with melanoma and other solid tumors. In collaboration with an interdisciplinary research group at Hopkins, Medarex/Bristol Myers-Squibb, and other medical institutions, it was found that patients with treatment-refractory advanced metastatic cancers could respond to blockade of the immune cell inhibitory receptor programmed death-1 (PD-1) or its partner molecule PD-L1 on tumor cells. Research led by Dr. Topalian has characterized the pharmacodynamics of anti-PD-1 and anti-PD-L1 drugs and has explored tumor molecular markers predictive of clinical response. Since animal models suggest that blockade of PD-1 and PD-L1 synergizes with cancer vaccines, Dr. Topalian has continued to search for optimal tumor target antigens, investigating mutated peptides, phosphorylated peptides, and structural interactions between T cell receptors and these antigens in collaboration with Dr. Roy Mariuzza at the University of Maryland. Combination treatment regimens of anti-PD-1/PD-L1 with other immune-modulating antibodies, kinase inhibitors, and epipigenetic therapy are under development.
Clinical Trial KeywordsDirector, Melanoma Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Selected PublicationsView all on Pubmed
Deng, L.; Langley, R.J.; Brown, P.H.; Xu, G.; Teng, L.; Wang, Q.; Gonzales, M.I.; Callender, G.G.; Nishimura, M.I.; Topalian, S.L.; Mariuzza, R.A. Structural basis for the recognition of mutant self by a tumor-specific, MHC class II-restricted T cell receptor. Nat Immunol. 2007 Apr;8(4):398-408.
Depontieu, F.R.; Qian, J.; Zarling, A.L.; McMiller, T.L.; Salay, T.M.; Norris, A.; English, A.M.; Shabanowitz, J.; Engelhard, V.H.; Hunt, D.F.; Topalian, S.L. Identification of tumor-associated, MHC class II-restricted phosphopeptides as targets for immunotherapy. Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12073-12078.
Brahmer, J.R.; Drake, C.G.; Wollner, I.; Powderly, J.D.; Picus, J.; Sharfman, W.H.; Stankevich, E.; Pons, A.; Salay, T.M.; McMiller, T.L.; Gilson, M.M.; Wang, C.; Selby, M.; Taube, J.M.; Anders, R.; Chen, L.; Korman, A.J.; Pardoll, D.M.; Lowy, I.; Topalian, S.L. 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 Jul 1;28(19):3167-3175.
Li, Y.; Depontieu, F.R.; Sidney, J.; Salay, T.M.; Engelhard, V.H.; Hunt, D.F.; Sette, A.; Topalian, S.L.; Mariuzza, R.A. Structural basis for the presentation of tumor-associated MHC class II-restricted phosphopeptides to CD4+ T cells. J Mol Biol. 2010 Jun 18;399(4):596-603.
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. PMC3568523.
Topalian SL, Hodi FS, Brahmer JR, et al. (30 authors). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443-54. PMC3544539.
Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian, SL et al.(26 authors). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J. Med 2012; 366:2455-65. PMC3563263
Deng L, Langley RJ, Wang Q, Topalian SL, Mariuzza RA. Structural insights into the editing of germline-encoded interactions between T cell receptor and MHC class II by VaCDR3. Proc Natl Acad Sci USA, 2012; 109:14960-5. PMC3443186.
Lipson EJ, Sharfman WH, Drake CG, Wollner I, Taube JM, Anders RA, Xu H, Yao S, Pons A, Chen L, Pardoll DM, Brahmer JR, Topalian SL. Durable cancer regression off-treatment and effective re-induction therapy with an anti-PD-1 antibody. Clin Cancer Res, 2013; 19:462-468. PMC3548952.
Lyford-Pike S, Pen S, Young GD, Taube JM, Westra WH, Akpeng B, Bruno TC, Richmon JD, Wang H, Bishop JA, Chen L, Drake CG, Topalian SL, Pardoll DM, Pai SI. Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res, 2013; 73:1733-41. PMC3602406.
Lipson EJ, Vincent JG, Loyo M, Kagohara LT, Luber BS, Wang H, Xu H, Nayar SK, Wang TS, Sidransky D, Anders RA, Topalian SL, Taube JM. PD-L1 expression in the Merkel cell carcinoma microenvironment: Association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunol Res, 2013; 1:54-63. PMC3548952.
Chen S, Li Y, Depontieu FR, McMiller TL, English AM, Shabanowitz J, Kos F, Sidney J, Sette A, Rosenberg SA, Hunt DF, Mariuzza RA, Topalian SL. Structure-based design of altered MHC II-restricted peptide ligands with heterogeneous immunogenicity. J Immunol 2013; 191:5097-106. PMC3888030.
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014;32:1020-30.
Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 2014; doi:10.1158/1078-0432.CCR-13-3271.
Activities & Honors
- Federal Technology Transfer Award, 2003
- American Association for Cancer Research;
- American Association of Clinical Oncology;
- American Association of Immunologists
- Society for Melanoma Research;
- Society for the Immunotherapy of Cancer
- Chief Scientific Officer, Melanoma Research Alliance