|SOM Address||Room 4M07 Cancer Research Building I|
Luke Pfannenstiel 2001 – 2009
Mechanisms of induction of human anti-tumor 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.
- Uram JN, Black CM, Flynn E, Huang L, Armstrong TD, Jaffee EM. Nondominant CD8 T cells are active players in the vaccine-induced antitumor immune response. J Immunol. 2011;186(7):3847-57. PMCID: 3162214.
- Weiss VL, Lee TH, Song H, Kouo TS, Black CM, Sgouros G, Jaffee EM, Armstrong TD. Trafficking of high avidity HER-2/neu-specific T cells into HER-2/neu-expressing tumors after depletion of effector/memory-like regulatory T cells. PLoS One. 2012;7(2):e31962. PMCID: 3281086.
- Le DT, Brockstedt DG, Nir-Paz R, Hampl J, Mathur S, Nemunaitis J, Sterman DH, Hassan R, Lutz E, Moyer B, Giedlin M, Louis JL, Sugar EA, Pons A, Cox AL, Levine J, Murphy AL, Illei P, Dubensky TW, Jr., Eiden JE, Jaffee EM, Laheru DA. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers: phase I studies of safety and immune induction. Clinical cancer research : an official journal of the American Association for Cancer Research. 2012;18(3):858-68. PMCID: 3289408.
- Lutz E, Yeo CJ, Lillemoe KD, Biedrzycki B, Kobrin B, Herman J, Sugar E, Piantadosi S, Cameron JL, Solt S, Onners B, Tartakovsky I, Choi M, Sharma R, Illei PB, Hruban RH, Abrams RA, Le D, Jaffee E, Laheru D. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation. Ann Surg. 2011;253(2):328-35. PMCID: 3085934.
- Zheng L, Foley K, Huang L, Leubner A, Mo G, Olino K, Edil BH, Mizuma M, Sharma R, Le DT, Anders RA, Illei PB, Van Eyk JE, Maitra A, Laheru D, Jaffee EM. Tyrosine 23 phosphorylation-dependent cell-surface localization of annexin A2 is required for invasion and metastases of pancreatic cancer. PLoS One. 2011;6(4):e19390. PMCID: 3084841.
- Zheng L, Xue J, Jaffee EM, Habtezion A. Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma. Gastroenterology. 2013;144(6):1230-40. PMCID: 3641650.
- Le DT, Lutz E, Uram JN, Sugar EA, Onners B, Solt S, Zheng L, Diaz LA, Jr., Donehower RC, Jaffee EM, Laheru DA. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. Journal of Immunotherapy. 2013;36(7):382-9. 3779664.