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Suzanne Louise Topalian, M.D.

Photo of Dr. Suzanne Louise Topalian, M.D.

Melanoma Program Director

Professor of Surgery

Female

Languages: English, French

Expertise: General Surgery, Melanoma, Skin Cancer

Research Interests: Mechanism-of-action of immune checkpoint pathways; clinical development of drugs and drug combinations modulating immune checkpoints in cancer therapy; identification of predictive biomarkers for the activity of immune checkpoint blocking drugs. ...read more

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Locations

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
Phone: 410-502-8218
Fax: 410-502-1958

Background

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.

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Titles

  • Melanoma Program Director
  • Associate Director, Bloomberg~Kimmel Institute for Cancer Immunotherapy
  • Professor of Surgery
  • Professor of Oncology

Departments / Divisions

Education

Degrees

  • MD, Tufts University School of Medicine (1979)

Residencies

  • Jefferson Medical College of Thomas Jefferson University / General Surgery (1985)

Fellowships

  • National Cancer Institute- NIH / Oncology (1989)

Research & Publications

Research Summary

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 Keywords

Director, Melanoma Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Selected Publications

View all on Pubmed

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. *co-corresponding author

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.

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.

Nghiem PT*, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling S, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL*, Cheever MA. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 2016; DOI:10.1056/NEHMoa1603702. *co-corresponding author

Activities & Honors

Honors

  • Federal Technology Transfer Award, 2003

Memberships

  • American Association for Cancer Research;
  • American Association of Clinical Oncology;
  • American Association of Immunologists
  • Society for Melanoma Research;
  • Society for the Immunotherapy of Cancer

Professional Activities

  • Chief Scientific Officer, Melanoma Research Alliance
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