Leisha Emens, M.D., Ph.D.
Phone: (410) 955-8964
Fax: (410) 614-8216
Titles
Associate Professor of Oncology
Schools/Degrees
M.D., Medicine, Baylor College of Medicine, Houston, TX
Ph.D., Cell Biology, Baylor College of Medicine, Houston, TX
Training
Clinical Fellow in Hematology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD
Senior Clinical and Research Fellow in Medical Oncology, Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD
Susan B. Komen Clinical Breast Cancer Fellowship, Johns Hopkins Oncology Center
Intern and Resident, Internal Medicine, University of Texas Southwestern Affiliated Hospitals, Parkland Memorial Hospital and Dallas VA Medical Center, Dallas, TX
Postdoctoral Research Fellow, Laboratory of Biological Chemistry, National Cancer Instutitute, National Institutes of Health, Bethesda, MD
Predoctoral Fellow, Baylor College of Medicine, Houston, TX
Certifications
Internal Medicine
Medical Oncology
Hematology
Clinical Interests
Medical Oncology
Breast Cancer
Research Summary
Dr. Emens develops and tests active vaccination strategies for breast cancer treatment that are optimally integrated with traditional anticancer therapies and newer biologically targeted therapies in additive or synergistic ways. She developed a genetically-modified, cell-based vaccine for breast cancer that secretes the immune-stimulating hormone granulocyte-macrophage colony-stimulating factor (GM-CSF), and first tested the vaccine in combination with low doses of Cyclophosphamide (CY) and Doxorubicin (DOX) in patients with Stage 4 breast cancer. In a mouse model of spontaneous breast cancer where the vaccine does not work, adding CY and DOX cures about 30% of tumor-bearing mice. This chemotherapy effect is largely due to the ability of CY to turn off a special type of immune cell (regulatory T cell) that keeps immune responses shut down. Analysis of patient samples on this trial demonstrated the vaccine alone to be active, and that it’s activity was enhanced by CY 200 mg/m2 and DOX 35 mg/m2—doses of CY higher than 200 mg/m2 inhibited the vaccine. Dr. Emens is now analyzing the sera of responding patients for novel targets of the vaccine-induced immune response for further study. She has also investigated the addition of monoclonal antibodies that target either the tumor itself (HER-2/neu), or the tumor microenvironment (vascular endothelial growth factor receptor 2 (VEGFR2) to chemotherapy-modulated vaccination. Both add futher to the antitumor effect of the vaccine. In particular, HER-2/neu-specific monoclonal antibodies augment antigen processing and presentation, resulted in higher numbers of CD8+ T cells after chemotherapy-modulated vaccination in the presence of the antibody. Based on these data, Dr. Emens has launched three clinical trials testing the HER-2/neu-specific monoclonal antibody Trastuzumab in combination with CY-modulated vaccination, two in patients with HER-2/neu-overexpressing breast cancer, and one in patients with breast cancer that does not overexpress HER-2/neu. The overall goal of Dr. Emens research is to elucidate mechanisms of immunoregulation in patients with breast cancer using the vaccine in combination with standard breast cancer drugs and novel therapeutics. These studies should identify novel drug targets and new therapies to improve breast cancer outcomes.
Journal Citations
Davis-Sproul, J. M., Harris, M. P., Davidson, N. E., Kobrin, B. J., Jaffee, E. M. & Emens, L. A. (2005). Cost-effective manufacture of an allogeneic GM-CSF-secreting breast tumor vaccine in an academic cGMP facility. Cytotherapy 7, 46-56.
Emens, L. (2008). Jump-Starting Tumor Immunity with Breast Cancer Therapeutics. In: Cancer Vaccines and Tumor Immunity, ed. J.W.H.B.D. Rimas Orentas: Johnson, John Wiley and Sons, Inc.
Emens, L. A. & Jaffee, E. M. (2005). Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res 65, 8059-64.
Emens, L. A. (2006). Editorial. Int Rev Immunol 25, 259-68.
Emens, L. A. (2006). Roadmap to a better therapeutic tumor vaccine. Int Rev Immunol 25, 415-43.
Emens, L. A. 2008. Chemotherapy and tumor immunity: an unexpected collaboration. Front Biosci 13:249-57.
Emens, L. A., Reilly, R. T. & Jaffee, E. M. (2005). Cancer vaccines in combination with multimodality therapy. Cancer Treat Res 123, 227-45.
Emens, L., Miller, KD, and Mehta, R. (2008). Physician Roles in Academia: The Physician–Scientist, Clinical Investigator, and Clinician-Educator. . In: Career Resources Guide for the American Society of Clinical Oncology., ed. L. Hutchins, Blayney, DW, Ochs, JS, and Schwartz, JE: ASCO, 150-164.
Emens, L.A. (2008). Cancer vaccines: on the threshold of success. Expert Opin Emerg Drugs 13, 295-308.
Kim, P.S., Armstrong, T.D., Song, H., Wolpoe, M.E., Weiss, V., Manning, E.A., Huang, L.Q., Murata, S., Sgouros, G., Emens, L.A., Reilly, R.T., and Jaffee, E.M. (2008). Antibody association with HER-2/neu-targeted vaccine enhances CD8 T cell responses in mice through Fc-mediated activation of DCs. J Clin Invest 118, 1700-1711.
Manning, E. A., J. G. Ullman, J. M. Leatherman, J. M. Asquith, T. R. Hansen, T. D. Armstrong, D. J. Hicklin, E. M. Jaffee, and L. A. Emens. 2007. A vascular endothelial growth factor receptor-2 inhibitor enhances antitumor immunity through an immune-based mechanism. Clin Cancer Res 13:3951-9.
Murata, S., Ladle, B. H., Kim, P. S., Lutz, E. R., Wolpoe, M. E., Ivie, S. E., Smith, H. M., Armstrong, T. D., Emens, L. A., Jaffee, E. M. & Reilly, R. T. (2006). OX40 costimulation synergizes with GM-CSF whole-cell vaccination to overcome established CD8+ T cell tolerance to an endogenous tumor antigen. J Immunol 176, 974-83.
Zellars, R.C., Stearns, V., Frassica, D., Asrari, F., Tsangaris, T., Myers, L., DiPasquale, S., Lange, J., Jacobs, L., Emens, L.A., Armstrong, D., Fetting, J., Garrett-Mayer, E., Davidson, N.E. and Wolff, A.C. (2009). Feasibility Trial of Partial Breast Irradiation with Concurrent Dose-Dense Doxorubicin and Cyclophosphamide in Early Stage Breast Cancer. J Clin Onc 27, 2816-2822.
Davis-Sproul, J., Harris, M. P., Davidson, N. E., Kobrin, B. J., Jaffee, E. M., & Emens, L. A. 2005. Cost-effective manufacture of an allogeneic GM-CSF-secreting breast tumor vaccine in an academic cGMP facility. Cytotherapy. 7:46-56.
Emens, L. A. 2005. Towards a breast cancer vaccine: the next steps. Expert Rev. Vaccines. 4:831-841.
Emens, L. A., & Jaffee, E. M. 2005. Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res. 65:8059-8064.
Ercolini, A. M., Ladle, B. H., Manning, E. A., Pfannenstiel, L. W., Armstrong, T. D., Machiels, J. P., et al. 2005. Recruitment of latent pools of high avidity CD8(+) T cells to the antitumor immune response. J. Exp. Med. 201:1591-1602.
