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 a mouse model of breast 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.
- The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach recently 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.
- 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:
- 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. HER-2/neu is a tumor rejection target in the HER-2/neu transgenic mouse model of breast cancer, Cancer Research 60:3569-3576, 2000. Pub Med Reference
- Machiels, J.P., Reilly, R.T., Emens, L., Ercolini, A., Okoye, F., and Jaffee, E.M. 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, 2001. Pub Med Reference
- 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. 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, 2001. Pub Med Reference
- Reilly, R.T., Machiels, J.P., Emens, L.A., Ercolin, A.M., Okoye, F.I., Lei, R.Y., Weintraub, D., and Jaffee ,E.M. 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, 2001. Pub Med Reference
- Ercolini, A.M., Machiels, J.-P., Chen, Yi Cheng, Slansky, J.E., Giedlen, M., Reilly, R.T., and Jaffee, E.M. 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, 2003. 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. 200:297-306, 2004. 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. 201:1591-1602, 2005. Pub Med Reference
- Laheru D, Jaffee EM. Immunotherapy for pancreatic cancer-science driving clinical progress. Nature Reviews Cancer, 5(6):459-467, 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 EM. 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 2008 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. Antibody association with HER-2/neu-targeted vaccine enhances CD8 T cell responses in mice through Fc-mediated activation of DCs. J Clin Invest 2008 May 1:118(5):1700-1711. Pub Med Reference
- Leao, IC; Ganesan, P; Armstrong, Todd; Jaffee, EM; Effective Depletion of Regulatory T Cells allows the Recruitments of Mesothelin-Specific CD8+ cells to the antitumor Immune Response Agains a Mesothelin-expressing Mouse Pancreatic Adenocarcinoma. Clinical and Translational Science. 2008 Vol.1, Issue 3, 228-239.
- Herman JM, Swartz MJ, Hsu CC, Winter J, Pawlik TM, Sugar E, Robinson R, Laheru DA, Jaffee E, Hruban RH, Campbell KA, Wolfgang CL, Asrari F, Donehower R, Hidalgo M, Diaz LA Jr, Yeo C, Cameron JL, Schulick RD, Abrams R. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreatico-duodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008 Jul 20;26 (21): 3503-10. Pub Med Reference
- Jones, S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Kamiyama H, Jimeno A, Hong SM, Fu G, Lin M, Calhoun ES, Kamiyama M, Walter K, Nikolskaya T, Nikolsky Y, Hartigan J, Smith DR, Hidalgo M, Leach SD, Klein AP, Jaffee EM, Goggins M, Maitra A, Iacobuzio-Donahue C, Eshleman JR, Kern SE, Hruban RH, Karchin R, Papadopoulous N, Parmigiani G, Vogelstein B, Velculescu VE, Kinzler KW. Core signaling pathways in human pancreatic cancer revealed by global genomic analyses. Science. 2008 Sep 26; 321(5897):1801-6. Pub Med Reference
- Miyashita T, Shah FA, Marti GP, Armstrong TD, Wang J, Bonde P, Gibson MK, Yoshimura K, Montgomery EA, Duncan M, Jaffee EM, Harmon JW. Vaccine impedes the development of reflux-induced esophageal cancer in a surgical rat model: efficacy of the vaccine in a post-Barrett's esophagus setting. Dig Dis Sci. 2008 Nov;53(11):2858-67. Epub 2008 Mar 15. Pub Med Reference
- Disis, ML; Bernhard, H; Jaffee, EM. Review: Use of tumor-responsive T cells as cancer treatment. The Lancet. 2009 Feb21; 373: 673-83. Pub Med Reference
- Kitamura M, Murata S, Ueki, T, Mekata E, Reilly RT, Jaffee E, Tani T. OX40 costimulation can abrogate Foxp3+ regulatory T cell-mediated suppression of antitumor immunity. Int Journ of Cancer. 135, 630-638, 2009. Pub Med Reference
- Emens L, Asquith J, Leatherman J, Kobrin B, Petrik S, Laiko M, Levy J, Daphtary M, Biedrzycki B, Wolff A, Stearns V, Disis M, Xiaobu Y, Piantadosi S, Fetting J, Davidson N, Jaffee EM. 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. Journ of Clin Onc, 2009. Epub ahead of print on 10/5/09. Pub Med Reference
Other graduate programs in which Dr. Jaffee participates:
