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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: Human anti-tumor immunity; biomarkers for response to anti-PD-1 therapies; combination cancer therapies based on anti-PD-1.

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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
  • 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

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.

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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