A5018392015- Immunotherapy and Immune Responses
- Cervical Cancer and HPV Research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Hepatitis B Virus Studies
- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Immune cells in cancer
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- Lipid Membrane Structure and Behavior
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- Chemokine receptors and signaling
- Glycosylation and Glycoproteins Research
- Liver physiology and pathology
- Hepatitis C virus research
- Phagocytosis and Immune Regulation
- Immune Response and Inflammation
- Viral Infections and Outbreaks Research
- Reproductive System and Pregnancy
- Cytomegalovirus and herpesvirus research
University of Groningen
2016-2025
University Medical Center Groningen
2016-2025
Target (United States)
2002-2018
Dialyse Centrum Groningen
2005-2015
Hanze University of Applied Sciences
2014
Gujarat Institute of Desert Ecology
2012
Tyrolean Cancer Research Institute
2010
European Molecular Biology Laboratory
2006
Dana-Farber Cancer Institute
1984
Utrecht University
1982-1983
Ovarian cancer patients with intra-tumoral CD3+ T-lymphocytes in primary tumor tissue have a better prognosis. This study aims to analyze the presence and relative influence of three important T-lymphocyte subsets, tumor-infiltrating CD8+ cytotoxic (CTL), CD45R0+ memory T-lymphocytes, FoxP3+ regulatory (Treg), omental metastases ovarian cancer. The number CD8+, CD45R0+, was determined by immunohistochemistry on micro array containing and/or obtained at debulking surgery from 306 FIGO stage...
Abstract Purpose: Therapeutic vaccination with human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides (SLP) is effective against HPV16-induced high-grade vulvar vaginal intraepithelial neoplasia (VIN/VaIN). However, clinical nonresponders displayed weak CD8+ T-cell reactivity. Here, we studied if imiquimod applied at the vaccine site could improve reactivity, efficacy, safety of HPV16-SLP (ISA101). Experimental Design: A multicenter open-label, randomized controlled trial was...
Abstract The prognosis of ovarian cancer, the primary cause death from gynecological malignancies, has only modestly improved over last decades. Immunotherapy is one new treatment modalities explored for this disease. To investigate safety, tolerability, immunogenicity and obtain an impression clinical activity a p53 synthetic long peptide (p53‐SLP) vaccine, twenty patients with recurrent elevation CA‐125 were included, eighteen whom immunized 4 times 10 overlapping p53‐SLP in Montanide...
Human papilloma virus (HPV)-induced cervical cancer constitutively expresses viral E6/E7 oncoproteins and is an excellent target for T cell-based immunotherapy. However, not all tumor-infiltrating cells confer equal benefit to patients, with epithelial being superior stromal cells.To assess whether the cell biomarker CD103 could specifically discriminate beneficial antitumor cells, association of clinicopathological variables outcome was analyzed in TCGA data set (n = 304) by...
The high efficacy of therapeutic cancer vaccines in preclinical studies has yet to be fully achieved clinical trials. Tumor immune suppression is a critical factor that hampers the desired antitumor effect. Here, we analyzed combined effect vaccine and receptor tyrosine kinase inhibitor sunitinib. Sunitinib was administered intraperitoneally, alone or combination with intramuscular immunization using viral vector based composed Semliki Forest virus replicon particles encoding oncoproteins E6...
Human papillomavirus (HPV) infection is the major cause of (pre)malignant cervical lesions. We previously demonstrated that Vvax001, a replication-incompetent Semliki Forest virus (SFV) vaccine encoding HPV type 16 (HPV16) E6 and E7, induced potent anti-E6 -E7 cytotoxic T-cell responses. Here, we investigated clinical efficacy Vvax001 in patients with HPV16-positive intraepithelial neoplasia grade 3 (CIN3). Patients newly diagnosed CIN3 were eligible for participation. received immunizations...
Abstract Doxorubicin entrapped within conventional liposomes (200 nm in diameter; lip‐Dox) has major toxic effects on liver macrophages of the rat for a considerable period time following i.v. administration, with respect to both specific phagocytic capacity and cell numbers. At different time‐points after injection lip‐Dox or free doxorubicin, radiolabeled, negatively charged, “empty” test were injected. Phagocytic was determined by isolating measuring amount macrophage‐associated...
The purpose of the current phase II single-arm clinical trial was to evaluate whether pretreatment with low-dose cyclophosphamide improves immunogenicity a p53-synthetic long peptide (SLP) vaccine in patients recurrent ovarian cancer. Patients cancer elevated serum levels CA-125 after primary treatment were immunized four times p53-SLP vaccine. Each immunization preceded by administration 300 mg/m2 intravenous as means affect regulatory T cells (Tregs). Vaccine-induced p53-specific...
// Eveline M. Dijkgraaf 1 , Saskia J.A.M. Santegoets An K.L. Reyners 2 Renske Goedemans Hans W. Nijman 3 Mariëtte I.E. van Poelgeest 4 Arien R. Erkel 5 Vincent T.H.B.M. Smit 6 Toos A.H.H. Daemen 7 Jacobus J.M. der Hoeven Cornelis Melief 8 Marij J.P. Welters Judith Kroep 1, * Sjoerd H. Burg Department of Medical Oncology, Leiden University Center, 2333 ZA, Leiden, The Netherlands Clinical Center Groningen, 9713 GZ, Gynecologic Gynecology, Radiology, Pathology, Microbiology, Immunohematology...
Abstract Purpose: Tumor-infiltrating lymphocytes (TIL) are associated with a better prognosis in high-grade serous ovarian cancer (HGSC). However, it is largely unknown how this prognostic benefit of TIL relates to current standard treatment surgical resection and (neo-)adjuvant chemotherapy. To address outstanding issue, we compared infiltration unique cohort patients advanced-stage HGSC primarily treated either surgery or neoadjuvant Experimental Design: Tissue microarray slides containing...
CD103+ tumor-infiltrating lymphocytes (TIL) have been linked to specific epithelial infiltration and a prolonged survival in high-grade serous ovarian cancer (HGSC). However, whether these cells are induced as part of an ongoing anti-HGSC immune response or represent non-specifically expanded resident mucosal remains largely unknown. In this study, we first confirmed that TIL from HGSC were predominantly localized the epithelium strongly correlated with improved prognosis. We further...
A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 E7. Twelve participants with a history cervical intraepithelial neoplasia were included. Four cohorts three treated per dose level, ranging from 5 × 105 to 2.5 108...
M2-like tumor-associated macrophages promote tumor progression by establishing an immunosuppressive microenvironment. The phenotype and activity of are related to their mitochondrial metabolism. Thus, we studied if drugs targeting metabolic pathways can repolarize from M2 into M1-like or prevent M0-to-M2 polarization. selected clinically approved in clinical trials target M2-specific pathways: fatty acid oxidation (Perhexiline Trimetazidine), glutaminolysis (CB-839), PPAR activation (HX531),...
Abstract Purpose: To evaluate if serum cytokine levels could be used as diagnostic or prognostic markers in ovarian cancer. Experimental Design: A bead array was done to simultaneously analyze 14 cytokines the sera of 187 cancer patients with complete clinicopathologic data and follow-up, 45 benign tumors, 50 healthy controls. Serum well-known tumor marker CA-125 were routinely measured all patients. Results: CA-125, interleukin 6 (IL-6), IL-7, IL-10 elevated compared tumors. Analyzing...
Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (T(regs)) might be involved in the failure of immune system to control development HPV-induced cancer. We investigated frequencies, phenotype activity T(regs) patients with neoplasia. CIN showed increased CD4(+)/CD25(high) cell frequencies peripheral blood CD4(+) fraction. These represent as demonstrated by their low...