A5069267169- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cervical Cancer and HPV Research
- Virus-based gene therapy research
- Colorectal and Anal Carcinomas
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Immune cells in cancer
- Viral gastroenteritis research and epidemiology
- Viral-associated cancers and disorders
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- Transplantation: Methods and Outcomes
- Single-cell and spatial transcriptomics
- Head and Neck Cancer Studies
- vaccines and immunoinformatics approaches
- Genital Health and Disease
- Hepatitis B Virus Studies
- Cytomegalovirus and herpesvirus research
- Nanoplatforms for cancer theranostics
- Epigenetics and DNA Methylation
- Reproductive tract infections research
- Cancer Cells and Metastasis
Leiden University Medical Center
2016-2025
Oncode Institute
2020-2025
Justus-Liebig-Universität Gießen
2020
German BioImaging – Gesellschaft für Mikroskopie und Bildanalyse
2020
Leiden University
2007-2019
Society for Immunotherapy of Cancer
2014
Data Harbor (United States)
2014
Dutch Blood Transfusion Society
2010
Zero to Three
2010
Institute of Haematology and Blood Transfusion
2007-2010
Vulvar intraepithelial neoplasia is a chronic disorder caused by high-risk types of human papillomavirus (HPV), most commonly HPV type 16 (HPV-16). Spontaneous regression occurs in less than 1.5% patients, and the rate recurrence after treatment high.We investigated immunogenicity efficacy synthetic long-peptide vaccine women with HPV-16-positive, high-grade vulvar neoplasia. Twenty grade 3 were vaccinated three or four times mix long peptides from HPV-16 viral oncoproteins E6 E7 incomplete...
Abstract Purpose: The study aims to evaluate the effect of a human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides vaccine on antigen-specific T-cell response in cervical cancer patients. Experimental Design: Patients with resected HPV16-positive were vaccinated an overlapping set comprising sequences HPV16 oncoproteins emulsified Montanide ISA-51. HPV16-specific immune responses analyzed by evaluating magnitude, breadth, type, polarization proliferation assays,...
Anti–CTLA-4 treatment increases the diversity of melanoma-specific CD8 T cell response.
Abstract Monocytes attracted by tumor-induced chronic inflammation differentiate to APCs, the type of which depends on cues in local tumor milieu. In this work, we studied influence human cervical cancer cells monocyte differentiation and showed that majority either hampered dendritic cell or skewed their toward M2-like macrophages. Blocking studies revealed M2 was caused tumor-produced PGE2 IL-6. TGF-β, IL-10, VEGF, macrophage colony-stimulating factor did not play a role. Notably, these...
Current therapy of gynecologic malignancies consists platinum-containing chemotherapy. Resistance to is associated with increased levels interleukin (IL)-6 and prostaglandin E2 (PGE(2)), 2 inflammatory mediators known skew differentiation monocytes tumor-promoting M2 macrophages. We investigated the impact cisplatin carboplatin on 10 different cervical ovarian cancer cell lines as well ability tumor cells affect function cocultured in vitro. Treatment or potency induce IL-10-producing...
Abstract Purpose: To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 E7 long peptide vaccine administered to end-stage cervical cancer patients. Experimental Design: Three groups patients (in total n = 35) were s.c. vaccinated with HPV16 combined or separated from overlapping peptides in Montanide ISA-51 adjuvant, four times at 3-week intervals. Group 1 received 300 μg/peptide single site group 2 100 one limb second limb. 3 separate injections...
Abstract Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m −2 , to receive either mimicking diet (FMD) or their regular for 3 days prior during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite fact dexamethasone omitted FMD group. A...
Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer more vulnerable to it. This pilot study examines the feasibility STF its on tolerance in a homogeneous patient group with early breast (BC). Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized fast 24 h before after commencing chemotherapy, or eat according guidelines...
Therapeutic vaccination against HPV16 is effective with chemotherapy for advanced cervical cancer patients.
There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under umbrella of Association Immunotherapy coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After consultation period, two-stage approach was designed to harmonize phenotype. In first step, international consortium 23...
Regulatory T cell (Treg)-mediated immunosuppression is considered a major obstacle for successful cancer immunotherapy. The association between clinical outcome and Tregs being studied extensively in trials, but unfortunately, no consensus has been reached about (a) the markers (b) gating strategy required to define human this context, making it difficult draw final conclusions. Therefore, we have organized an international workshop on detection functional testing of with leading experts...
Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models analyses of human melanoma patients, we show that cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion cells activated endothelial cells, which a pre-requisite extravasation....
One half of a group 20 patients with human papillomavirus type 16 (HPV16)-induced vulvar intraepithelial neoplasia grade 3 displayed complete regression (CR) after therapeutic vaccination HPV16 E6/E7 synthetic long peptides. Patients relatively larger lesions generally did not display CR. To investigate immune correlates treatment failure, were grouped according to median lesion size at study entry, and HPV16-specific immunity was analyzed different time points by complementary immunological...
No consensus has been reached on how to determine if an immune response detected based raw data from ELISPOT assay. The goal of this paper is enable investigators understand and readily implement currently available methods for determination. We describe empirical statistical approaches, identifying the strengths limitations each approach allow readers rationally select apply a scientifically sound method appropriate their specific laboratory setting. Five representative approaches were...
Because of their important role in the maintenance self-tolerance, CD4 + regulatory T cells prevent autoimmune diseases but also curtail efficacy cell immune responses against cancers. We now show that this suppressive action is not limited to cancers displaying tumor-associated self antigens, such as melanomas, extends human papillomavirus (HPV)-positive cervical express foreign tumor antigens. HPV-specific isolated from lymph node biopsies cancer patients were found suppress proliferation...
Abstract Background Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical are found many women worldwide. The HPV16 encoded oncoproteins E6 and E7 tumor-specific targets for the adaptive immune system permitting development of an HPV16-synthetic long peptide (SLP) vaccine with excellent treatment profile animal models. Here, we determined toxicity, safety, immunogenicity efficacy SLP patients advanced or recurrent HPV16-induced carcinoma. Methods...
Abstract Purpose: The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal and can serve as a target for immunotherapy. safety immunogenicity of synthetic long peptide (p53-SLP) vaccine were investigated patients treated metastatic cancer. Experimental Design: Ten vaccinated twice with set 10 overlapping p53-SLP phase I/II trial. Both the breadth, magnitude, polarization vaccine-induced p53-specific T cells was evaluated blood samples drawn before after...
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 Purpose: Human papillomavirus (HPV)–associated oropharyngeal squamous cell cancer (OPSCC) has a much better prognosis than HPV-negative OPSCC, and this is linked to dense tumor immune infiltration. As the viral antigens may trigger potent immunity, we studied relationship between presence of intratumoral HPV-specific T-cell responses, contexture in microenvironment, clinical outcome. Experimental Design: To purpose, an in-depth analysis tumor-infiltrating cells prospective cohort 97...
New treatments based on combinations of standard therapeutic modalities and immunotherapy are potential use, but require a profound understanding immune modulatory properties therapies. Here, the impact (chemo)radiotherapy system cervical cancer patients was evaluated. Thirty with were treated external beam radiation therapy (EBRT), using conventional three-dimensional or intensity modulated without constraints for bone marrow sparing. Serial blood sampling immunomonitoring performed before,...