Research team

Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Expertise

Experimental and clinical expertise in isolated lung perfusion in vivo (only available as cooperative research project).

Translational research on the novel combination of chemotherapy and anti-CD70 immunotherapy to improve treatment outcome in non-small cell lung cancer. 01/10/2016 - 30/09/2020

Abstract

Non-small cell lung cancer (NSCLC) retains its position as the most lethal type of cancer with around 1.3 million deaths per year worldwide and a marginally improving 5-year overall survival rate which remains below 20%, pointing to the need for new therapeutic options. Immunotherapy, in which the patient's immune system is used to selectively eliminate cancer cells, is considered a very promising candidate. Results of the recently approved immunotherapeutic agent nivolumab underscore the potential of immunotherapy in NSCLC, but also leave room for improvement. This study will focus on the CD70-CD27 signaling pathway as an interesting novel target to enhance anti-tumoral immune responses in NSCLC in combination with low doses of chemotherapy. CD70 is a member of the tumor necrosis factor family and its expression is normally restricted to activated T and B cells. Constitutive expression of CD70 by tumor cells can facilitate immune evasion by increasing the amount of suppressive regulatory T cells, inducing T cell apoptosis and skewing T cells towards T cell exhaustion. Previously, we have detected constitutive overexpression of CD70 in NSCLC tumor specimens, also in patients that lack other targeted treatment options. This CD70 expression can be exploited by CD70-targeting antibody-dependent cellular cytotoxicity (ADCC)-inducing antibodies. Our preliminary data show that the combination of anti-CD70 therapy with low doses of chemotherapy significantly increases cytotoxicity of the drug, compared to single treatment regimens. The main objective of the current project proposal is to rationally design and to preclinically evaluate a combination therapy of chemotherapy with CD70-targeted immunotherapy as a novel treatment option for patients with NSCLC.

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Expression and role of dipeptidyl peptidases and related peptidases in acute lung injury. 01/01/2015 - 31/12/2018

Abstract

Acute lung injury remains the third major cause of mortality worldwide, and it is assumed that excessive inflammatory responses could be involved. The precise role of dipeptidyl peptidases (DPPs; a family of enzymes that cleave off dipeptides from the amino terminus of peptides) in the pathophysiology of acute lung injury is poorly understood. Taken broadly, the DPP family consists of DPPIV, fibroblast activation protein alpha (FAP), prolyl oligopeptidase (PREP), DPP8 and DPP9. DPPIV inhibitors are used in the treatment of diabetes type 2, but evidence for other roles of DPPIV is also emerging. Despite a presumed role of individual peptidases in lung disease, knowledge on DPPs in acute lung injury remains limited. Previously, we have shown that DPPIV inhibitors protect against lung ischemia-reperfusion induced injury. Apart from that, we discovered that DPP9 has a role in macrophage activation, which is an important component of acute lung injury. The current project aims to explore the hypothesis that DPPIV, DPP9 and related peptidases play a role in the pathophysiology of acute lung injury. We will study the expression of DPPs in both an infectious and a non-infectious mouse model of acute lung injury. Subsequently, we will determine the effect of DPPIV inhibition on the outcome, and will assess whether DPPs have a role in lung macrophages. We will compare the animal findings with measurements in human tissue to study the translational potential of our results.

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Pathogenetic role of endothelial nitric oxide synthase uncoupling in ischemia- and reperfusion injury of the lung. 01/10/2014 - 30/09/2016

Abstract

The objective of our research is to determine whether the process of eNOS uncoupling can also be demonstrated in lung tissue after ischemia and reperfusion injury (IRI). In the first part of the project, experimental techniques were developed in order to detect free radical production during IRI using electron paramagnetic resonance. A murine model of pulmonary IRI was also developed. We are currently working on the effect of eNOS itself, and eNOS uncoupling, on free radical generation during pulkmonary IRI. Our final aim is to develop therapeutic strategies to tackle pulmonary IRI in patients undergoing complex surgery such as cardiopulmonary bypass, lung transplantation and isolated lung perfusion.

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Scientific work ASTARC Department, Antwerp Surgical Training and Research Center, discipline-thoracic and vascular surgery. 03/10/2011 - 02/10/2014

Abstract

This project represents a formal service agreement between UA and on the other hand UZA. UA provides UZA research results mentioned in the title of the project under the conditions as stipulated in this contract.

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Feasibility and safety of a WT1-targeted cancer vaccine in patients with malignant mesothelioma and locally advanced breast cancer: an open label phase I trial. 01/01/2011 - 31/12/2013

Abstract

The Wilms' tumor 1 (WTI) protein has been shown to be a universal tumor antigen overexpressed in many tumors, including malignant mesothelioma and breast carcinoma. In view of the T cell immunogenicity of WTI-derived peptides, immunostimulatory dendritic cells loaded with WT1 antigen hold promise as a universal, yet patient-specific, polyepitope cancer vaccine to treat residual disease. Here, autologous monocyte-derived dendritic cells will be transfected with mRNA coding for the entire WT1 antigen and injected intradermally as a cellular cancer vaccine in mesothelioma and breast cancer patients as adjuvant treatment after optimal debulking or after neo-adjuvant chemotherapy. In this project, we want to investigate the safety, feasibility and immunogenicity of such WTI-targeted cancer vaccine in an open-label phase I trial.

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    Ion mobility high resolution mass spectrometer: a strong tool for fragile structures. 22/07/2010 - 21/07/2015

    Abstract

    This project has two general objectives: (1) Increase the research potential of the UA by introduction of new state of the art techniques for the analysis of fragile molecular structures by using the novel ion mobility capabilities that have recently been integrated with high-mass high-resolution Q-TOF mass spetrometry ("Synapt", waters). (2) Maintain the current capacity to obtain Q-TOF data by replacing an existing system.

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    Influence of melphalan isolated lung perfusion on the (phospho)-proteome. 01/07/2009 - 31/12/2013

    Abstract

    This project studies the regulation, phosphorylation and adduct formation of proteins in tumors upon melphalan treatment. LC-MS methods will be developed using a representative cell culture. An animal model (induced lung tumors) will be treated by melphalan isolated lung perfusion prior to analysis of human samples. Final goal is the selection of candidate biomarkers ((phospho-)protein, melphalan-proteinadduct, ...) with prognostic value for the treatment of lung metastases by melphalan-ILuP.

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    Phase II Study of isolated lung perfusion combined with pulmonary metastasectomy for the treatment of patients with operable lung metastases from colorectal carcinoma, osteosarcoma or soft tissue sarcoma 01/08/2008 - 31/07/2010

    Abstract

    Due to its filtering capacity for the entire circulation, the lung is a common site for malignant disease. Among patients with metastic cancer, 20-30 % will have secondary spread to the lung according to necropsy series. The poor results of surgical resection of pulmanory metastases from osteogenic sarcomas, soft tissue sarcomas and colorectal adenocarcinomas are probably due to genetic drug resistance and the inability to achieve effective drug concentrations within the tumor mass. In this way, isolated lung perfusion can be a promising procedure for the treatment of tumors metastatic to the lungs which are surgically unresectable and unresponsive to conventional chemotherapy. It has the advantage of both selectively delivering an agent and diverting the venous effluent. This allows the drug to to be delivered in a higher dose without systemic complications.

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    Investigation on the presence of Chlamydia Pneumoniae in human atherosclerotic lesions. 01/01/1999 - 31/12/2000

    Abstract

    Search for the presence of Chlamydia Pneumoniae in patients with atherosclerotic lesions or aneurysmal disease of the aorta, coronary, carotid and femoral arteries and in control vessels without lesions by improved culture techniques and PCR. The PCR will be performed after different DNA extraction methods and in two different laboratories to exclude false positive results.

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      Isolated lung perfusion with chemotherapy in an in-vivo rat model for the treatment of pulmanory metastases. 01/10/1996 - 31/12/1997

      Abstract

      Due to its filtering capacity for the entire circulation, the lung is a common site for malignant disease. Among patients with metastic cancer, 20-30 % will have secondary spread to the lung according to necropsy series. The poor results of surgical resection of pulmanory metastases from osteogenic sarcomas, soft tissue sarcomas and colorectal adenocarcinomas are probably due to genetic drug resistance and the inability to achieve effective drug concentrations within the tumor mass. In this way, isolated lung perfusion can be a promising procedure for the treatment of tumors metastatic to the lungs which are surgically unresectable and unresponsive to conventional chemotherapy. It has the advantage of both selectively delivering an agent and diverting the venous effluent. This allows the drug to to be delivered in a higher dose without systemic complications.

      Researcher(s)

      Research team(s)

        Isolated lung perfusion with chemotherapy in an in-vivo rat model for the treatment of pulmanory metastases. 01/01/1996 - 31/12/1997

        Abstract

        Due to its filtering capacity for the entire circulation, the lung is a common site for malignant disease. Among patients with metastic cancer, 20-30 % will have secondary spread to the lung according to necropsy series. The poor results of surgical resection of pulmanory metastases from osteogenic sarcomas, soft tissue sarcomas and colorectal adenocarcinomas are probably due to genetic drug resistance and the inability to achieve effective drug concentrations within the tumor mass. In this way, isolated lung perfusion can be a promising procedure for the treatment of tumors metastatic to the lungs which are surgically unresectable and unresponsive to conventional chemotherapy. It has the advantage of both selectively delivering an agent and diverting the venous effluent. This allows the drug to to be delivered in a higher dose without systemic complications.

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          A randomized double-blind multicenter, placebo-controlled, parallel group study to evaluate daily intravenous infusions of Prostavasin. 01/01/1993 - 30/06/1994

          Abstract

          Double-blind, multicentric randomized study; patients with arterial ulcers who have inqerable peropheral vascular disease receive placebo or Prostavasin, evaluation by ulcer score.

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