Current Key Areas of Research
The Program in Cancer Immunology and Immunotherapy brings together experts in the fields of immunobiology, medicine, and oncology to explore the interaction between the immune system and cancer.
Building on their findings, program members are advancing new strategies that use the exquisite specificity of the body's natural defenses to destroy tumors with minimal toxicity to healthy tissues.
Program researchers work between the lab and the clinic investigating the cellular arms of the immune system for new treatment opportunities. Their efforts are advancing the areas of:
- Experimentations, including therapeutic treatments with chemically-modified peptide-based vaccines that enforce the tumor-bearing animal’s immune defenses to attack the autologous/transplantable cancer cells.
- Glucocorticoid-guided immune pathways on cytokine-dependent NK-cell activation and homeostasis.
- NK cell-based adoptive therapies aiming at the involvement of innate immunity in cancer therapeutics directly but also indirectly at the interface of induction of adaptive antitumor immune responses.
- The potential of small molecule inhibitors and other effector molecules as therapeutic agents in combination with peptide-based vaccines.
- Gene-regulation of mesenchymal cell differentiation and regulation of tumor cell growth within the tumor stroma.
While there has been considerable success in decreasing overall cancer mortality rates through improved and earlier screening, there is a need for more sophisticated, targeted therapies that are able to specifically and effectively destroy cancer cells.
CIIC believes that clinical research in cancer cannot be considered as simply product development, but rather requires a systematic and academic approach to develop rational therapeutic strategies.
CIIC is currently exploring three therapeutic modalities.
- Vaccinations with single hybrid peptides encompassing the active region of the regulatory part of the MHC class II – associated Invariant chain (Ii-Key) chemically linked to a long peptide from HER-2/neu (p776-790) (patented by Antigen Express Inc., a subsidiary of Generex Biotechnology Corporation) in collaboration with Antigen Express.
- Vaccinations with multi long-peptide mixtures derived from various shared tumor antigens (in collaboration with several European Cancer Immunology Centers).
- Adoptive therapy with cytokine-activated NK cells from HLA-mismatched donors.
Infrastructure for systems biology Europe-Greece/Clinical Genomics
The CIIC is part of a consortium which participates in a multicenter translational study for identifying biomarkers for chronic diseases also including cancer. Such biomarkers detected in biological fluids and various types of cells will be useful acting as prognostic and predictive, but also as targets for therapeutic interventions.
Identification of immunogenic peptides to act as novel vaccine candidates from prostate cancer tumor specimens
The CIIC collaborates with IMMATICS a biotech company in Tuebingen Germany for the isolation and identification of tumor peptides from surgically excised prostate tumor specimens. These peptides are going to be tested for prevention and therapy of experimental tumors in mice before entering in phase I clinical trials.
Expression of CRD-BP, TET1 and TET2 in human mesenchymal cells from various sources
This project aims at investigating the role of the above genes in proliferation and metastatic potential of tumor cells. These genes but also other metabolites which belong to the molecular pathways dominated by the above genes may be used as therapeutic targets in combination with other signal transduction inhibitors.
Regulation of NK cell growth and function by glucocorticoids (GCs)
In this project we are investigating the role of GCs on the function and expansion potential of NK cells. In particular, we are interested in testing whether GCs enhance NK cell proliferation and also protect NK cells from cytokine-induced cell death without compromising their functional potential. To this end, we investigate how and if GCs affect the phenotype of NK cells in terms of NK cell activating receptors, maturation markers and chemokine receptors, in order to obtain info-rmation on the differential effects of GCs on different subpopulations of circulating NK cells and their possible impact on their clinical use in cancer treatment.
Identification of immune cells infiltrating tumors and in the peripheral blood as prognostic/predictive biomarkers in breast cancer
In this project we propose to explore the prognostic impact of tumor-infiltrating lymphocytes as well as macrophages in patients with breast carcinoma (BC). Our studies will include for the first time (i) prospective analyses to identify this immune profil in patients with newly-diagnosed BC with clinical follow-up and (ii) comparative quantification and phenotyping of circulating T lymphocytes responding to tumor antigens overexpressed in BC. We will compare peripheral with intra-tumoral immune markers for longitudinal follow-up . In addition, we will perform retrospective analyses to correlate the infiltrating immune phenotypes with clinical outcome in patients with BC who were treated between 2000 and 2008.
List of Research Studies and Funding Sources
- SFS Programme, NATO Scientific Affairs Division. Development of Immunodiagnostics in Greece (1987-1993), 700.000$
- Commission of the European Community. Medical Research Division "Cellular and Molecular Strategies for Immunotherapy of Cancer" , 324.000 EURO
- European Community. Mediterannean Programmes. "Production of monoclonal antibodies against normal and leukemic lymphocytes", 180.000 Euro
- EPET 2 (General Secretariat of Research and Technology), 300.000 Euro (1996-1999)
- Production of immunodiagnostic assays for the detection of hepatitis B and HIV 1,2. NATO Scientific Affairs Division 1995-2000, BF 6.000.000
- DG XVI through "PEP Attica". Development of Cancer Vaccines, 700.000 Euro (1996-2000)
- The European Commission through the General Secretariat of Research in Greece. Cancer Immunotherapy: Genetic modification of T lymphocytes and CD34+ stem cells with tumor specific chimeric receptors, 900.000 Euro (1998-2001)
- The European Commission through the General Secretariat of Research in Greece. Isolation and genetic manipulation of CD34+ stem cells for therapeutic use in BM transplantation, 800.000 Euro (1999-2001)
- The European Commission through 3rd Operational Program PEP of Attica (MIS 59605). Production of vaccines against cancer, 2.220.000 Euro (2001-2009)
- The General Secretariat of Research and Technology in the framework of ΕPΑΝ II ”Cancer immunotherapy: genetical modification of T lymphocytes and CD34+ progenitors with tumor antigen-specific chimeric receptors”; code no.97EKBAN2-19; period:1998-2002, 1.000.000 Euro
- The General Secretariat of Research and Technology in the framework of EPAN II “Use of Biosensors for the study of immunogenicity of tumor cells”; code no. 97-EL-34; period 1999-2003, 700.000 Euro
- The General Secretariat of Research and Technology in the framework of EPET “Modifications in the expression of genes and proteins in tumor cell lines overexpressing HER-2/neu”; code no. YB/3; period: 2003-2007, 1.000.000 Euro
- Bilateral Research Programmes between Greece and Germany funded by the General Secretariat of Research and Technology “Isolation and identification of immunogenic peptides eluted from tumor cells to be used in cancer immunotherapy” code no. GRI-0606-097; period :1997-2000, 70.000 Euro
- Bilateral Research Programmes between Greece and Germany funded by the General Secretariat of Research and Technology “ Generation of CD4+ T lymphocyte lines and clones recognizing immunogenic epitopes of HER-2/neu. Analysis of their role in the induction cytotoxic reactions against HER-2/neu overexpressing tumor cell lines” code no. GRI-037099; period: 1999-2002, 70.000 Euro
- The General Secretariat of Research and Technology in the framework of PENED “Production of natural killer cells genetically modified to recognize HER-2/neu overexpressing tumor cells” code no. 01ED55; period 2002-2005, 100.000 Euro
- The General Secretariat of Research and Technology in the framework of PENED “Immunotherapy against HER-2/neu+ tumors”; code no. 03ED113; period :2005-2009, 100.000 Euro
- The European Commission in the framework of BIOMED II (CIIC, collaborarting partner), “EUCAPS” code no. BMH4-CT98-3058; period: 1998-2002, 100.000 Euro
- The European Commission in the framework of QLRT-2001-00668; period: 2002-2005, 150.000 Euro
- The European Commission in the framework of Quality of Life and Management of Living Resources (CIIC, collaborarting partner), “ ENACT” code no. LSHC-CT-2004 503306; period 2005-2008, 150.000 Euro
- Phase I clinical study on vaccinating prostate cancer patients with an Ii-Key/HER-2/neu vaccine (code no. after approval from National Organization of Medicines : IS-107-01-06). Funded by Generex SA, 250.000 Euro
- Phase II clinical study on vaccinating breast cancer patients with 2 different Ii-Key/HER-2/neu vaccines (code no. after approval from National Organization of Medicines : IS-52/01-03-07). Funded by Generex SA, 550.000 Euro
- Phase I study on cellular immunotherapy with infusions of activated natural killer cells in non-small lung cancer (code no. code no. after approval from National Organization of Medicines : IS-89/01/06)
- Antigen Express Inc. In vitro and in vivo antitumor activities induced by Ii-Key/HER-2/neu(776-790) hybrid peptide. 1996-until now, 600.000 Euro
- ROCHE Hellas funded project: Effect of Trastuzumab therapy on the frequency of circulating regulatory T cells in HER-2/neu overexpressing breast cancer patients (2006-2007), 22.250 Euro
- EISAI funded project (ONT-IIS-0018-07): A Pre-Clinical Study for the Combined Immunotherapy of Lung Cancer by Elimination of Suppressor Cells Prior to NK Cell Adoptive Transfer (2008-2010), 23.805 USD
- ROCHE Hellas funded project: Combination of Trastuzumab therapy with HER-2/neu peptide vaccination in disease free HER-2/neu overexpressing breast cancer patients for prevention of recurrence (2008-2010), 20.000 Euro
- ROCHE Hellas funded project: Do shedded HER-ECD and/or HER-2/neu+ apoptotic bodies complexed with trastuzumab induce effective T cell responses? (2009-2010), 16.660 Euro
- Bilateral Research Programmes between Greece and Germany funded by the European Commission: “Immune signatures within the tumor and in the peripheral blood as prognostic/predictive biomarkers in breast cancer (acronym: ISPEBREAST)” (2013-2015), 250.000 Euro