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PhD candidate on the topic: immune imaging in cancer, FHML/School of Oncology and Developmental Biology/department of Internal Medicine

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Offered by:

Maastricht University

Research / Academic
Maastricht

Description:

 In this PhD project you will be working on imaging of immune cell infiltration in the tumor with respect to different immune inhibitory factors present in the tumor micro-environment.An important immune suppressive factor is hypoxia. Hypoxia in cancer is responsible for the selection of highly aggressive cancer cells that survive under hypoxic conditions and it protects cancer cells from elimination by the immune system.

Part of this project is the in vivo evaluation of hypoxia in the bone marrow of multiple myeloma patients by PET-CT based hypoxia imaging and confirmation by immunohistochemical analysis of bone marrow biopsies from MM patients.

In addition to this clinical imaging in MM patients we have set out to develop a pre-clinical in vivo non-invasive nanobody-based imaging strategy to detect immune cell infiltration in relation to different immunosuppressive factors of the tumor micro-environment. For these pre-clinical studies we will make use of existing solid tumor as well as hematological tumor animal models.

Nanobodies, also known as single heavy chain only antibodies (VHHs), are small (15kDa) antibody fragments consisting of a single monomeric variable antibody domain and thereby harbor the full antigen-binding capacity. They are engineered from single heavy chain-only antibodies that naturally occur in camelids. Nanobodies are about 10 times smaller than conventional human or murine antibodies, which make them particularly suitable as targeting probes against antigens in isolated locations, such as tumors, where tissue penetration is critical. Nanobodies are easily generated against any antigen of interest by immunization of an alpaca. Additionally, nanobodies are stable and display high affinity. This in combination with their small size make them attractive for therapeutic use as well as for imaging studies. When chemically linked to different imaging probes, these VHHs can be utilized for different in vivo as well as ex vivo imaging strategies (PET-CT, confocal microscopy, multi-photon microscopy, mass spectrometric microscopy)

Nanobodies can be generated to all kinds of antigens like tumor antigens, hypoxia markers and most interesting for this project to immune cells. This approach can be utilized as a read out system for evaluation of therapeutic strategies that increase immune cell infiltration as well as a tool to correlate therapeutic effect to immune cell infiltration.

As nanobodies are small in size they can also be genetically or chemically linked to form bispecific nanobodies or linked to immune-active molecules. Thereby nanobodies can form a platform for new anti-tumor immunotherapeutic strategies. 

Requirements:

Candidates will be judged on the basis of the requirements outlined below. To be considered, candidates should make sure that their application letter demonstrates how they meet these requirements.

Applicants should have a master degree in science preferably in Chemistry with an interest for cancer immunotherapy. Applicants with a master degree in Biology, Health Sciences or Medicine with preferably prior experience in chemistry and/or small animal models are also encouraged to apply. You should display perseverance, a driven, independent and curious nature, great analytical skills, international orientation, and excellent verbal and written communication skills in English.

Salary Benefits:

Temporary employment for 4 years. Your salary would be € 2.266,- gross per month in the first year up to € 2.897,- gross per month in the fourth year according to the PhD-candidate salary scale. Each year an evaluation will take place.

The terms of employment of Maastricht University are set out in the Collective Labour Agreement of Dutch Universities (CAO). Furthermore, local UM provisions also apply. For more information look at the website www.maastrichtuniversity.nl > Support > UM employees.

Work Hours:

38 hours per week

Address:

Minderbroedersberg 4