Elizabeth M. Jaffee

Department Affiliation: Primary: Oncology;
Degree: M.D., New York Medical College
Rank: Professor
Telephone Number: 410-955-2957
Fax Number: 410-614-8216
Email Address: ejaffee@jhmi.edu
School of Medicine Address: Room 4M07, Cancer Research Bldg., 1650 Orleans Street, Baltimore, Maryland 21231

Mechanisms of induction of mouse and human antitumor immune responses

Current projects include:

The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors. This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development.
The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed . This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases.
The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics.

Representative Publications:

Emens, L.A., Asquith, J.M., Leatherman, J.M., Kobrin, B.J., Petrik, S., Laiko, M., Levi, J., Daphtary, M.M., Biedrzycki, B., Wolff, A.C., Stearns, V., Disis, M.L., Ye, X., Piantadosi, S., Fetting, J.H., Davidson, N.E., Jaffee, E.M. Timed sequential treatment with cyclophosphamide, doxorubicin, and an allogeneic granulocyte-macrophage colony-stimulating factor-secreting breast tumor vaccine: a chemotherapy dose-ranging factorial study of safety and immune activation. J Clin Oncol. 27(35): 5911-8, 2009. Pub Med Reference

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. Recruitment of latent pools of high avidity CD8(+) T cells to the antitumor immune response, J Exp Med. 201(10):1591-602, 2005. Pub Med Reference

Jones, S., Zhang, X., Parsons, D.W., Lin, J.C., Leary, R.J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.M., Fu, B., Lin, M.T., Calhoun, E.S., Kamiyama, M., Walter, K., Nikolskaya, T., Nikolsky, Y., Hartigan, J., Smith, D.R., Hidalgo, M., Leach, S.D., Klein, A.P., Jaffee, E.M., Goggins, M., Maitra, A., Iacobuzio-Donahue, C., Eshleman, J.R., Kern, S.E., Hruban, R.H., Karchin, R., Papadopoulous, N., Parmigiani, G., Vogelstein, B., Velculescu, V.E., Kinzler, K.W. Core signaling pathways in human pancreatic cancer revealed by global genomic analyses. Science 321(5897):1801-6. Pub Med Reference

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., Jaffee, E.M. 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(5):1700-11, 2008. Pub Med Reference

Laheru, D., Jaffee, E.M. Immunotherapy for pancreatic cancer-science driving clinical progress. Nat Rev Cancer. 5(6):459-67, 2005. Pub Med Reference

Laheru, D., Lutz, E., Burke, J., Biedrzycki, B., Solt, S., Onners, B., Tartakovsky, I., Nemunaitis, J., Le, D., Sugar, E., Hege, K., Jaffee, E.M. 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. Clin Cancer Res. 14(5):1455-63. Pub Med Reference

Leao, I.C., Ganesan, P., Armstrong, T. Jaffee, E.M. Effective depletion of regulatory T cells allows the recruitment of mesothelin-specific CD8 T cells to the antitumor immune response against a mesothelin-expressing mouse pancreatic adenocarcinoma. Clin Transl Sci. 1(3):228-39, 2008. Pub Med Reference

Lutz, E., Yeo, C.J., Lillemoe, K.D., Biedrzycki, B., Kobrin, B., Herman, J., Sugar, E., Piantadosi, S., Cameron, J.L., Solt, S., Onners, B., Tartakovsky, I., Choi, M., Sharma, R., Illei, P.B., Hruban, R.H., Abrams, R.A., Le, D., Jaffee, E., Laheru, D. A lethally irradiated allogeneic granulocyte-macrophange colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma: a Phase II trial of safety, efficacy, and immune activation. Ann Surg. 253(2):328-35, 2011. Pub Med Reference

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. 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(3):297-306, 2004. Pub Med Reference

Zheng, L., Foley, K., Huang, L., Leubner, A., Mo, G., Olino, K., Edil, B.H., Mizuma, M., Sharma, R., Le, D.T., Anders, R.A., Illei, P.B. Van Eyk, J.E., Maitra, A., Laheru, D., Jaffee, E.M. Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer. PLoS One. 6(4):e19390, 2011. Pub Med Reference

Uram, J.N., Black, C.M., Flynn, E., Huang, L., Armstrong, T.D., Jaffee, E.M. Nondominant CD8 T cells are active players in the vaccine-induced antitumor immune response. J Immunol. 186(7):3847-57, 2011. Pub Med Reference

Other graduate programs in which Dr. Jaffee participates:

Cellular and Molecular Medicine Graduate Program
Immunology

Quick Links