The Netherlands Cancer Institute (NKI) – Antoni van Leeuwenhoek hospital (AVL) is a recognized comprehensive cancer center combining a cancer research institute and a specialized hospital under one roof. Within the NKI scientists and clinicians to work together, forming integrated teams that can rapidly translate new knowledge into prototype therapies and trial them in the clinic. This close collaboration, coupled with world-class scientists and clinicians, highly motivated students and outstanding facilities has made the NKI an internationally recognized center of excellence in cancer research and treatment.
The NKI researchers have extensive experience concerning the role of tumor and virus-specific cytotoxic T-cells, T-helper cells, T-regulatory cells and antigen presenting cells in tumor-specific immunity. Prof Schumacher has been PI of several projects concerning tumour immunology not only in HPV related disease, but also in melanoma. Several DNA vaccines have been developed including one based on the BARF epitope for melanoma as one with HPV epitope. All facilities needed for analysis and expansion of HPV16-specific T-cell responses (including all state-of-the-art immunological technologies currently available) from blood and tumor specimens are available. Furthermore, HPV typing and immunohistochemistry, including the quantitative assessment of TIL by 4-color confocal microscopy, is performed on a routine basis in house.
This project will be carried out by the departments of gynae-oncology and clinical oncology of NKI and fits in a longstanding program of immunotherapy of cancer. The colleagues within the departments have extensive experience concerning the role of tumor and virus-specific cytotoxic T-cells, T-helper cells, T-regulatory cells and antigen presenting cells in tumor-specific immunity. Prof Kenter has been PI of the phase I and II clinical trials and was involved in the development of the synthetic long HPV 16 E6 and E7 peptide vaccine (SLP) with the group of Prof. C. Melief. This group has growing reputation for its innovative approaches using HPV immunotherapy for treatments of (pre)cancerous lesions of the ano-genital region. All facilities needed for the organization of a multinational multicenter clinical trial are available. NKI has recognized surgical and medical expertise that attracts fair numbers of patients and well established experience exists with immunotherapy and chemotherapy. The research group has recently completed three phase I clinical trials in which end-stage cervical carcinoma patients were vaccinated with an HPV16 synthetic long peptide (SLP) vaccine as well as two phase II trials in which patients with resected cervical cancer or vulva intraepithelial neoplasia grade 3 (VIN3) were vaccinated with the HPV16 SLP vaccine. Notably, in order to perform all these studies a company, AmBTU, was founded and will give access to new, improved vaccine formats for HPV E7/E6 DNA vaccines.
Role within the project
Prof. Gemma Kenter will act as project leader of WP5 in which two clinical trials in advanced cervical carcinoma patients will investigate the effect of immunotherapy added to standard therapy consisting of chemo-radiotherapy in patients with locally advanced or chemotherapy in metastasised/recurrent carcinoma of the cervix.
In NKI, which is the research unit of the Dutch cancer center, she will rely on the analyses of the immunological responses after immunotherapy as well as on assessments of the role of the micro-environment as a predictor for response to chem.-immunotherapy will be studied by dr. ES Jordanova.