- Medical School, National University of Athens, Athens, Greece, 1980 (M.D.)
- Department of, McGill University, Montreal, Quebec, 1982 (Post Doctoral Research Associate, Medicine)
- University of Ottawa, Ottawa, Ontario, 1986 (Residency, Pediatrics)
- University of Ottawa, Ottawa, Ontario, 1987 (Fellow, Pediatric Hematology/Oncology)
- University of Minnesota, Minneapolis,1990 (Fellow, Pediatric Hematology/Oncology & BMT)
- University of Minnesota, Minneapolis, 1991 (Post Doctoral Research Associate, Pediatrics)
- First Place Award, University of Minnesota Pediatric Fellows' Research Symposium, 1990
- Irvine McQuarrie Research Scholar Award, 1992-1994
- Young Investigator Award, American Society of Pediatric Hematology/Oncology, 1992
- Clinical Oncology Career Development Award, American Cancer Society, 1993-1996
- Louise Thomas Endowed Chair In Pediatric Cancer Research, 2005
Tumor-derived chaperone proteins (or heat shock proteins) are unique mediators of specific anti-tumor immunity when such proteins are purified from tumor tissue. We have developed a novel method that efficiently enriches for multiple chaperone complexes from tumor lysates using free solution isoelectric focusing (FS-IEF). Reproducibly and in numerous murine models, we have documented that vaccination with these Chaperone Rich Cell Lysates (CRCL) is more effective than immunization with purified individual chaperones such as HSP70 and GRP94/gp96, two heat shock proteins (HSPs) currently used in clinical immunotherapy trials. The antigenicity of CRCL can be augmented further by loading them onto dendritic cells (DCs) resulting in protection against murine tumors even in the setting of pre-existing disease. In addition to the antigen carrying capacities, CRCL have potent immunostimulatory effects on DCs. As adjuvants CRCL provide danger signals enhancing the immunogenicity leukemia cells undergoing apoptosis following drug treatment.
Research efforts are currently focused on studying the immunostimulatory activities of HSPs particularly in the form of CRCL. Our goal is to generate sufficient and convincing pre-clinical data to move CRCL vaccines into the clinical setting. We are continuing our studies in various murine models in order to understand further the mechanisms of action of CRCL vaccines. In parallel we have initiated in vitro studies examining the effects of human derived CRCL on human cells so we can establish efficacy and safety. Ongoing studies are 1) Characterizing the peptide antigen repertoire of CRCL vaccine derived from specific tumors. 2) Studying the in vivo synergistic effects of CRCL vaccine/adjuvant with drugs that induce apoptosis. 3) Biochemically characterizing human tumor derived CRCL, evaluating its effects on human DCs and examining the potential of human tumor derived CRCL-pulsed DCs to generate tumor specific CTLs.
Larmonier N, Merino D, Nicolas A, Cathelin D, Besson A, Bateman A, Solary E, Martin F, Katsanis E, Bonnotte B. Apoptotic, necrotic, or fused tumor cells: An equivalent source of antigen for dendritic cell loading. Apoptosis. 2006 (E-publication).
Larmonier N, Marron M, Zeng Y, Cantrell J, Romanoski A, Sepassi M, Thompson S, Chen X, Andreansky S, Katsanis E. Tumor-derived CD4(+)CD25 (+) regulatory T cell suppression of dendritic cell function involves TGF-beta and IL-10. Cancer Immunol Immunother. 2006 (E-publication).
Chen X, Zeng Y, Li G, Larmonier N, Graner MW, Katsanis E. Peritransplantation vaccination with chaperone-rich cell lysate induces antileukemia immunity. Biol Blood Marrow Transplant. 12(3):275-83, 2006.
Ramanathapuram LV. Hahn T. Graner MW. Katsanis E. Akporiaye ET. Vesiculated alpha-tocopheryl succinate enhances the anti-tumor effect of dendritic cell vaccines. Cancer Immunology, Immunotherapy. 55(2):166-77, 2006.
Zeng Y. Graner MW. Thompson S. Marron M. Katsanis E. Induction of BCR-ABL-specific immunity following vaccination with chaperone-rich cell lysates derived from BCR-ABL+ tumor cells. Blood. 105(5):2016-22, 2005.
Graner MW. Likhacheva A. Davis J. Raymond A. Brandenberger J. Romanoski A. Thompson S. Akporiaye E. Katsanis E. Cargo from tumor-expressed albumin inhibits T-cell activation and responses. Cancer Research. 64(21):8085-92, 2004.
Jason Wright (MSRP 2008): "Modulation of tumor induced regulatory T cells by killer dendritic cells."
Elaine Hutchinson (MSRP 2013): "Influence of Selected Vitamin E Compounds on Immune Cell Subsets in a Mammary Carcinoma Model."
Jaime Faulkner (MSRP 2017): "Blood Cytokine Levels Pre and Post MHC-Mismatched Bone Marrow Transplantation in Mice Pre-Treated with Bendamustine"
Jason Wright (Class of 2012): "Modulation of Treg FoxP3 transcription factor and suppressive function by killer dendritic cells."
Cecilia Machado, 2016: 2017 "Bendamustine as a conditioning agent"