Research Paul Van Schil

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.

Researcher(s)

• Promoter: Smits Evelien
• Co-promoter: Lardon Filip
• Co-promoter: Pauwels Patrick
• Co-promoter: Rolfo Christian
• Co-promoter: Van Schil Paul

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Adriaensen Dirk
• Co-promoter: De Meester Ingrid
• Co-promoter: Kumar-Singh Samir
• Co-promoter: Lambeir Anne-Marie
• Co-promoter: Van Schil Paul

Research team(s)

• Laboratory of cell biology and histology

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Van Schil Paul
• Co-promoter: Cos Paul
• Fellow: Gielis Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

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).

Researcher(s)

• Promoter: Van Schil Paul
• Co-promoter: Cos Paul
• Fellow: Gielis Jan

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Van Schil Paul

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Berneman Zwi
• Co-promoter: Germonpre Paul
• Co-promoter: Huizing Manon
• Co-promoter: Peeters Marc
• Co-promoter: Van de Velde Ann
• Co-promoter: Van Schil Paul
• Co-promoter: Van Tendeloo Vigor

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Sobott Frank
• Co-promoter: Guisez Yves
• Co-promoter: Lemière Filip
• Co-promoter: Maes Bert
• Co-promoter: Moens Luc
• Co-promoter: Tavernier Serge
• Co-promoter: Van Ostade Xaveer
• Co-promoter: Van Schil Paul
• Co-promoter: Wijnants Marc
• Co-promoter: Witters Erwin

Research team(s)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Lemière Filip
• Co-promoter: Van Schil Paul

Research team(s)

Project type(s)

• Research Project

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)

• Promoter: Van Schil Paul

Research team(s)

• Antwerp Surgical Training, Anatomy and Research Centre (ASTARC)

Project type(s)

• Research Project

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.

Researcher(s)

• Promoter: Ieven Margareta
• Co-promoter: Van Schil Paul
• Co-promoter: Vrints Christiaan

Research team(s)

Project type(s)

• Research Project

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)

• Promoter: Van Schil Paul

Research team(s)

Project type(s)

• Research Project

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)

• Promoter: Van Schil Paul
• Co-promoter: Eyskens Erik J M G

Research team(s)

Project type(s)

• Research Project

Abstract

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

Researcher(s)

• Promoter: Van Schil Paul

Research team(s)

Project type(s)

• Research Project