Elizabeth M. Jaffee, MD Professor of Oncology Johns Hopkins University Baltimore, Maryland                   Genes, Vaccines, and Immune Checkpoints:  An All Out Attack On Pancreatic Cancer 2009 Immunology Conference at: The Historic Stanley Hotel Concert Hall Estes Park, Colorado September 8, 2009   6:00 p.m.   Elizabeth Jaffee, M.D.  Professor of Oncology Title of Presentation: Genes, vaccines and immune checkpoints: an all out attack on  pancreatic cancer Biosketch: B.A. 1981, Brandeis; M.D. 1985, New York Medical College Research Interests: Dr. Jaffee is an internationally recognized leader in the development of immune based therapies for the treatment of pancreatic and breast cancers.  She is the first recipient of the Dana and Albert “Cubby” Broccoli Professorship in Oncology at the Sidney Kimmel Cancer Center at Johns Hopkins.  She is also a member of the Graduate Programs in Immunology, Pharmacology, and Cell and Molecular Medicine.   Dr. Jaffee’s research is focused on the development of novel vaccine approaches that overcome immune tolerance to developing pancreatic and breast cancers.  Dr. Jaffee develops concepts in animal models that are translated into innovative Phase I and II clinical trials.   Dr. Jaffee’s pre-clinical and clinical work has been funded by the NCI SPORE program, the NCI sponsored NCDDG grant mechanism, and RO1s.  Dr. Jaffee is also the Medical Director of our Good Manufacturing Practices facility, which produces clinical grade biologics for testing in cancer patients.  Dr. Jaffee also serves as a Deputy Director of the new Institute for Translational and Clinical Research at Johns Hopkins. Dr. Jaffee has developed combinatorial vaccine approaches in mouse models that are actively being tested in patients in “proof of principle” clinical trials.  Specifically, Dr. Jaffee has pioneered the development of a granulocyte-macrophage colony stimulating factor (GM-CSF) secreting whole tumor cell approach for the treatment of patients with pancreatic and breast cancers.  She has developed the HER-2/neu transgenic mouse model of breast cancers for identifying mechanisms of host immune tolerance that are barriers to effective anti-cancer immunization.  Her lab reported the role of regulatory T cells in inhibiting effective high avidity T cell activation.  More recently, she has developed a novel set of animal reagents to study the specific molecular signals that regulate T cell avidity under conditions of T cell activation and down regulation.  Dr. Jaffee’s group has completed 3 clinical trials testing the vaccine alone and in combination with T regulatory cell inhibitory agents in patients with pancreatic cancer. Using patient reagents, she has developed both functional and proteomic approaches to identify antigens that are the targets of both T cell and humoral responses.   Using these approaches, her laboratory has identified a number of pancreatic cancer antigenic targets that are being validated as targets of the immune response in Phase II clinical trials. Tehse antigens are also being evaluated for their biologic role in cancer development.  Dr. Jaffee’s vaccine concepts are also being testing in patients with breast cancers. Selected Publications: Reilly, R.T., Gottlieb, M.B.C., Ercolini, A.M., Machiels, J.-P., Kane, C.E., Okoye, F.I., Muller, W.J., Dixon, K.H., and Jaffee, E.M.  (2000) HER-2/neu is a tumor rejection target in the HER-2/neu transgenic mouse model of breast cancer. Cancer Research 60:3569-3576.  Machiels, J.P., Reilly, R.T., Emens, L., Ercolini, A., Okoye, F., and Jaffee, E.M. (2001)  Cyclophos- phamide, Doxorubicin, and Paclitaxel enhance the antigen-specific antitumor immune response of GM-CSF secreting whole cell vaccines in tolerized mice. Cancer Research 61:3689-3697.  Jaffee, E.M., Hruban, R.H., Biedrzycki, B., Laheru, D., Schepers, K., Sauter, P.R., Goemann, M., Coleman, J., Grochow, L., Donehower, R.C., Lillemoe, K.D., O'Reilly, S., Abrams, R.A., Pardoll, D.M., Cameron, J.L., and Yeo, C.J. (2001)  A novel allogeneic GM-CSF-secreting tumor vaccine for pancreatic cancer: A phase I trial of safety and immune activation. Journal of Clinical Oncology 19:145-156. Reilly, R.T., Machiels, J.P., Emens, L.A., Ercolin, A.M., Okoye, F.I., Lei, R.Y., Weintraub, D., and Jaffee ,E.M. (2001) The collaboration of both humoral and cellular HER-2/neu- targeted immune responses is required for the complete eradication of HER-2/neu expressing tumors. Cancer Research 61-880-883. Ercolini, A.M., Machiels, J.-P., Chen, Yi Cheng, Slansky, J.E., Giedlen, M., Reilly, R.T., and Jaffee, E.M. (2003) Identification and characterization of the immunodominant rat HER-2/neu MHC class I epitope presented by spontaneous mammary tumors from HER-2/neu transgenic mice. J. Immunol. 170:4273-4280. Thomas, A.M., Santarsiero, L.M., Lutz, E.R., Armstrong, T.D., Chen, Y.-C., Huang, L.-Q,, Laheru, D.A., Goggins, M., Hruban, R.H., and Jaffee, E.M. (2004) Mesothelin specific CD8+ T cell responses provide human evidence of in vivo cross-priming by antigen presenting cells in vaccinated pancreatic cancer patients. J. Exp. Med. 200:297-306. Ercolini, A.M., Ladle, B.H., Manning, E.A., Pfannenstiel, L.W., Armstrong, T.D., Machiels, J.-P., Bieler, J.G., Emens, L.A., Reilly, R.T., and Jaffee, E.M. (2005) Recruitment of latent pools of high avidity CD8+ T cells to the antitumor immune response. J. Exp. Med. 201:1591-1602. Laheru D, Jaffee EM. (2005) Immunotherapy for pancreatic cancer-science driving clinical progress. Nature Reviews Cancer. 5(6):459-467. Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, Tartakovsky I, Nemunaitis J, Le D, Sugar E, Hege K, Jaffee EM. (2008) Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Cancer Therapy: Clin Can Res Mar l:14(5):1455-1463. Kim PS, Armstrong TD, Song H, Wolpoe ME, Weiss V, Manning EA, Huang LQ, Murata S, Sgouros G, Emens LA, Reilly RT, Jaffee EM. (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 May 1:118(5):1700-1711.