 Emmanuel Katsanis, MD
Contact Information:
Education:
- National University of Athens, 1980
Research:
Tumor and Transplantation Immunology.
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 c haperone r ich c ell l ysates (CRCL) is more effective than immunization with purified individual chaperones such as HSP 70 and GRP 94/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 continue 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.
Publications:
- Zeng Y, Feng H, Graner MW, Katsanis E. Tumor-derived chaperone-rich cell lysates activate dendritic cells and elicit potent anti-tumor immunity. Blood, 101:4485-4491, 2003.
- Feng H, Zeng Y, Graner MW, Likhacheva A, Katsanis E. Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate anti-tumor immunity. Blood, 101:245-252, 2003.
- Feng H, Zeng Y, Graner MW, Katsanis E. Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells. Blood, 100:4108-4115, 2002.
- Feng H, Zeng Y, Whitesell L, Katsanis E. Stressed apoptotic tumor cells express heat shock proteins and elicit tumor specific immunity. Blood, 97:3505-3512, 2001.
Peer-reviewed publications
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