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Ymittos Athens, Greece

Sakorafas G.H.,National and Kapodistrian University of Athens | Tsiotos G.G.,Metropolitan Hospital | Korkolis D.,Saint Savas Cancer Hospital | Smyrniotis V.,National and Kapodistrian University of Athens
Surgical Oncology | Year: 2012

Pancreatic cancer (PC) is a highly lethal disease. Despite advances regarding the safety and long-term results of pancreatectomies, early diagnosis remains the only hope for cure. This necessitates the implementation of an intensive screening program (based mainly on modern imaging), which - given the incidence of PC - is not cost effective for the general population. However, this screening program is recommended for individuals at high-risk for PC development. Indications for screening include the following three clinical settings: hereditary cancer predisposition syndromes associated with PC, hereditary pancreatitis and familial pancreatic cancer syndrome. The aim of this strategy is to identify pre-invasive (precursor) lesions, which are curable. Surgery is recommended in the presence of recognizable lesion on imaging lesions. Partial (anatomic) pancreatectomy - depending on the location of the suspicious lesion - is the most widely accepted type of surgical intervention in this setting; occasionally, however, total pancreatectomy may be required, in carefully selected patients. Despite that experience still remains limited, there is evidence that this aggressive strategy allows early detection of neoplastic lesions, thereby improving the effectiveness of surgery and prognosis. © 2010 Elsevier Ltd. All rights reserved. Source

Anastasopoulou E.A.,Cancer Immunology and Immunotherapy Center | Voutsas I.F.,Cancer Immunology and Immunotherapy Center | Keramitsoglou T.,Helena Venizelou Maternity Hospital | Gouttefangeas C.,University of Tubingen | And 5 more authors.
Cancer Immunology, Immunotherapy | Year: 2015

Recently, several types of immunotherapies have been shown to induce encouraging clinical results, though in a restricted number of patients. Consequently, there is a need to identify immune biomarkers to select patients who will benefit from such therapies. Such predictive biomarkers may be also used as surrogates for overall survival (OS). We have recently found correlations between immunologic parameters and clinical outcome in prostate cancer patients who had been vaccinated with a HER-2/neu hybrid polypeptide vaccine (AE37) and received one booster 6 months post-primary vaccinations. Herein, we aimed to expand these retrospective analyses by studying the predictive impact of HLA-A*24 and HLA-DRB1*11 alleles, which are expressed at high frequencies among responders in our vaccinated patients, for clinical and immunological responses to AE37 vaccination. Our data show an increased OS of patients expressing the HLA-DRB1*11 or HLA-A*24 alleles, or both. Vaccine-induced immunological responses, measured as interferon γ (IFN-γ) responses in vitro or delayed-type hypersensitivity reactions in vivo, were also higher in these patients and inversely correlated with suppressor elements. Preexisting (i.e., before vaccinations with AE37) levels of vaccine-specific IFN-γ immunity and plasma TGF-β, among the HLA-A*24 and/or HLA-DRB1*11 positive patients, were strong indicators for immunological responses to AE37 treatment. These data suggest that HLA-DRB1*11 and HLA-A*24 are likely to be predictive factors for immunological and clinical responses to vaccination with AE37, though prospective validation in larger cohorts is needed. © 2015, Springer-Verlag Berlin Heidelberg. Source

Iliopoulou E.G.,Cancer Immunology and Immunotherapy Center | Kountourakis P.,Saint Savas Cancer Hospital | Kountourakis P.,Bank of Cyprus Oncology Center | Karamouzis M.V.,Saint Savas Cancer Hospital | And 7 more authors.
Cancer Immunology, Immunotherapy | Year: 2010

HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2-4 doses of activated NK cells from two relative donors. Donor's CD56+ cells were cultured for 20-23 days with interleukin-15 (IL-15) and hydrocortisone (HC) and administered intravenously between chemotherapy cycles. Premedication with corticosteroids and/or H1 inhibitors was allowed. Sixteen patients (performance status 0-1) with adenocarcinoma (n = 13) or squamous cell carcinoma (n = 3) at stage IIIb (n = 5) or IV (n = 11) receiving 1st (n = 13) or 2nd (n = 3) line treatment were enrolled. Fifteen patients received 2-4 doses of allogeneic activated NK cells (0.2-29 × 10 6/kg/dose, median 4.15 × 106/kg/dose). No side effects (local or systemic) were observed. At a median 22-month follow-up (range, 16.5-26 months) 2 patients with partial response and 6 patients with disease stabilization were recorded. Median progression free survival and overall survival were 5.5 and 15 months, respectively. A 56% 1-year survival and a 19% 2-year survival were recorded. In conclusion, repetitive infusions of allogeneic, in vitro activated and expanded with IL-15/HC NK cells, in combination with chemotherapy are safe and potentially clinically effective. © 2010 Springer-Verlag. Source

Perez S.A.,Cancer Immunology and Immunotherapy Center | Kallinteris N.L.,Antigen Express Inc. | Bisias S.,Saint Savas Cancer Hospital | Tzonis P.K.,Cancer Immunology and Immunotherapy Center | And 6 more authors.
Clinical Cancer Research | Year: 2010

Purpose: Active immunotherapy is emerging as a potential therapeutic approach for prostate cancer. We conducted the first phase I trial of an Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine (AE37) with recombinant granulocyte macrophage colony-stimulating factor as adjuvant in patients with HER-2/neu+ prostate cancer. The primary end points of the study were to evaluate toxicity and monitor patients' immune responses to the vaccine. Experimental Design: Thirty-two HER-2/neu+, castrate-sensitive, and castrate-resistant prostate cancer patients were enrolled. Of these, 29 patients completed all six vaccination cycles with AE37. Immunologic responses in the total patient population were monitored by delayed-type hypersensitivity and IFN-γ ELISPOT and intracellular staining. Regulatory T-cell (Treg) frequency and plasma HER-2/neu and transforming growth factor-â levels were also determined. Immunologic responses were also analyzed among groups of patients with different clinical characteristics. Local/systemic toxicities were monitored throughout the study. Results: Toxicities beyond grade 2 were not observed. Seventy-five percent of patients developed augmented immunity to the AE37 vaccine and 65% to the unmodified AE36 peptide as detected in the IFN-γ-based ELISPOT assay. Intracellular IFN-γ analyses revealed that AE37 elicited both CD4+ and CD8+ T-cell responses. Eighty percent of the patients developed a positive delayed-type hypersensitivity reaction to AE36. Additionally, significant decreases could be detected in circulating Treg frequencies, plasma HER-2/neu, and serum transforming growth factor-β levels. Patients with less extensive disease developed better immunologic responses on vaccination. Conclusion: AE37 vaccine is safe and can induce HER-2/neu-specific cellular immune responses in patients with castrate-sensitive and castrate-resistant prostate cancer, thus emphasizing the potential of AE37 to target HER-2/neu for the immunotherapy of prostate cancer. ©2010 AACR. Source

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