ISPIC is a Marie Sklodowska-Curie Innovative Training Network (MSCA-ITN) on Image-Guided Surgery (IGS) and personalized postoperative immunotherapy to improving cancer in the Horzion2020 program of the European Union. In total, 20 Early Stage Researchers (ESRs) will be appointed by the ISPIC consortium for 12, 18, 24 or 36 months (PhD positions) depending on the role.
ISPIC project summary
The goal of this project is the implementation of an interdisciplinary and intersectoral cross-training program to develop a biomaterial-based encapsulated defined library of immunotherapeutic biomolecules as postoperative treatment as part of a novel cancer management strategy.
The hypothesis is that if we can develop a personalized strategy for cancer management of IGS combined with postoperative combination immunotherapy, we would be implementing a revolutionary imaging and therapeutic approach to target distal metastases.
• First key objective – to define subsets of immunoregulatory gene signatures for disease monitoring and to monitor efficacy of immunotherapy combinations incorporated into biomaterial-based platforms
• Second key objective – to optimise the biomaterial platform to encapsulate a small library of defined immune reagents for more accurate and timely delivery of the payload to its intended target either as NPs or as MPs
• Third key objective – to optimise the cancer management process of IGS followed by postoperative immunotherapy so that we can ultimately provide a lifetime of protection against cancer by utilising the body’s own immune response
The hypothesis is that if we can develop a personalized strategy for cancer management of IGS combined with postoperative combination immunotherapy, we would be implementing a revolutionary imaging and therapeutic approach to target distal metastases.
• First key objective – to define subsets of immunoregulatory gene signatures for disease monitoring and to monitor efficacy of immunotherapy combinations incorporated into biomaterial-based platforms
• Second key objective – to optimise the biomaterial platform to encapsulate a small library of defined immune reagents for more accurate and timely delivery of the payload to its intended target either as NPs or as MPs
• Third key objective – to optimise the cancer management process of IGS followed by postoperative immunotherapy so that we can ultimately provide a lifetime of protection against cancer by utilising the body’s own immune response
The Consortium
The consortium consists of partners from both academia and industry with excellent scientific qualifications in multiple disciplines:
• PERC – Percuros, Leiden, the Netherlands – Dr. Alan Chan
• LUMC – Leiden University Medical Center – Dr. Alex Vahrmeijer, Prof. Ferry Ossendorp
• TUD – Technical University of Delft – Prof. Boudewijn Lelieveldt, Prof. Marcel Reinders
• UC – University of Camerino – Dr. Piera di Martino, Dr. Roberta Censi
• TECO – TECObiosciences GmbH, Germany – Dr. Nadja Prang
• UVA – University of Amsterdam – Dr. Hong Zhang
• UB – University of Bergen, Norway – Prof. Emmet McCormack
• HH – Haukeland Hospital, Norway – Dr. Line Bjorge
• EPFL – Ecole Polytechnique Fédérale de Lausanne, Switzerland – Prof. Elena Dubikovskaya
• US – University of Sheffield, United Kingdom – Prof. Claire Lewis, Dr. Munitta Muthana, Dr. Russell Hughes
• MAAS – University of Maastricht, the Netherlands – Prof. Ron Heeren
• JENA – Jenacell, Germany – Dr. Dana Kralisch
• MEDRES – Medres, Germany – Stefan Wecker, Prof. Mathias Hoehn
• Erasmus University Rotterdam, the Netherlands – Prof. Clemens Lowik
• PERC – Percuros, Leiden, the Netherlands – Dr. Alan Chan
• LUMC – Leiden University Medical Center – Dr. Alex Vahrmeijer, Prof. Ferry Ossendorp
• TUD – Technical University of Delft – Prof. Boudewijn Lelieveldt, Prof. Marcel Reinders
• UC – University of Camerino – Dr. Piera di Martino, Dr. Roberta Censi
• TECO – TECObiosciences GmbH, Germany – Dr. Nadja Prang
• UVA – University of Amsterdam – Dr. Hong Zhang
• UB – University of Bergen, Norway – Prof. Emmet McCormack
• HH – Haukeland Hospital, Norway – Dr. Line Bjorge
• EPFL – Ecole Polytechnique Fédérale de Lausanne, Switzerland – Prof. Elena Dubikovskaya
• US – University of Sheffield, United Kingdom – Prof. Claire Lewis, Dr. Munitta Muthana, Dr. Russell Hughes
• MAAS – University of Maastricht, the Netherlands – Prof. Ron Heeren
• JENA – Jenacell, Germany – Dr. Dana Kralisch
• MEDRES – Medres, Germany – Stefan Wecker, Prof. Mathias Hoehn
• Erasmus University Rotterdam, the Netherlands – Prof. Clemens Lowik
The Job Vacancies
ESR 1
Employer: HH (Haukeland Hospital)
PhD Reg.: UB (University of Bergen)
Duration: 36 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details WP1.1. Develop surgical models of ovarian cancer for application to image-guided surgery.
Objectives: To further develop our in-house orthotopic surgical ovarian cancer PDX model for surgical intervention. Ovarian tumour biopsies (including ascites fluid) and whole blood, under debulking surgery and informed consent, will be harvested.
Expected Results: The ovarian tumours will be dissociated, and implanted in recipient mice to provide a model of improved surgical resection by intraoperative, tumour-specific fluorescence-based imaging.
Planned secondments: to LUMC to learn surgical techniques (3 months), to PERC to work on targeted probes for surgery (1 month) and to MAAS to look at new biomarkers or pathways identified at higher resolution MSI (2 months).
Employer: HH (Haukeland Hospital)
PhD Reg.: UB (University of Bergen)
Duration: 36 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details WP1.1. Develop surgical models of ovarian cancer for application to image-guided surgery.
Objectives: To further develop our in-house orthotopic surgical ovarian cancer PDX model for surgical intervention. Ovarian tumour biopsies (including ascites fluid) and whole blood, under debulking surgery and informed consent, will be harvested.
Expected Results: The ovarian tumours will be dissociated, and implanted in recipient mice to provide a model of improved surgical resection by intraoperative, tumour-specific fluorescence-based imaging.
Planned secondments: to LUMC to learn surgical techniques (3 months), to PERC to work on targeted probes for surgery (1 month) and to MAAS to look at new biomarkers or pathways identified at higher resolution MSI (2 months).
ESR 2
Employer: LUMC (Leiden University Medical Center)
PhD Reg. n.a.
Duration: 24 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details WP1.2. Develop immune competent models for breast and colorectal cancer for application toIGS and immunotherapy.
Objectives: To further develop our in-house syngeneic breast and colorectal cancer rodent models for both surgical intervention and adjuvant immunotherapy.
Expected Results: Immunocompetent syngeneic (C57BL/6J background) mouse models with relevance for surgery and adjuvant immunotherapy.
Planned secondments: to HH to work together on optimising surgical methods (3 months), to MAAS to look at new biomarkers or pathways identified at higher resolution MSI (2 months), to PERC to work on targeted probes for surgery (1 month).
Employer: LUMC (Leiden University Medical Center)
PhD Reg. n.a.
Duration: 24 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details WP1.2. Develop immune competent models for breast and colorectal cancer for application toIGS and immunotherapy.
Objectives: To further develop our in-house syngeneic breast and colorectal cancer rodent models for both surgical intervention and adjuvant immunotherapy.
Expected Results: Immunocompetent syngeneic (C57BL/6J background) mouse models with relevance for surgery and adjuvant immunotherapy.
Planned secondments: to HH to work together on optimising surgical methods (3 months), to MAAS to look at new biomarkers or pathways identified at higher resolution MSI (2 months), to PERC to work on targeted probes for surgery (1 month).
ESR 3
Employer: TUD (Technical University of Delft)
PhD Reg. n. a.
Duration: 12 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details WP1.3. New techniques for network analysis combining multiple large-scale expression studies in blood with Protein-Protein Interaction (PPI) data.
Objectives: Use state-of-art computational approaches (combined with MSI data from WP1.4) to identify those immune genes that are also relevant in humans.
Expected Results: Identified gene profiles before and after cancer surgery and with surgery in non-cancer subjects.
Planned secondments: to MAAS to integrate new pathway findings into the PPI database (2 months), toJENA to define the immune regulatory gene profiles in designing the assays (2 months).
Employer: TUD (Technical University of Delft)
PhD Reg. n. a.
Duration: 12 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details WP1.3. New techniques for network analysis combining multiple large-scale expression studies in blood with Protein-Protein Interaction (PPI) data.
Objectives: Use state-of-art computational approaches (combined with MSI data from WP1.4) to identify those immune genes that are also relevant in humans.
Expected Results: Identified gene profiles before and after cancer surgery and with surgery in non-cancer subjects.
Planned secondments: to MAAS to integrate new pathway findings into the PPI database (2 months), toJENA to define the immune regulatory gene profiles in designing the assays (2 months).
ESR 4
Employer: MAAS (University of Maastricht)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details: WP1.4. High Resolution MSI: Elucidation of local molecular signalling pathways on complex biological surfaces.
Objectives: MSI will be employed as a high resolution in situ technique to identify new biomarkers.
Expected Results: New and novel insights into pathways involved in tumour immunology.
Planned secondments: to PERC to learn about product development (1 month), to LUMC to correlate MSIwith conventional histology (1 month), to TUD to integrate and map out the immune regulatory pathways derived from MSI (1 month).
Employer: MAAS (University of Maastricht)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP1
Identification of PRECLINICAL immune gene signatures before and after surgery and during adjuvant immunotherapy (Activity type: Research)
Task details: WP1.4. High Resolution MSI: Elucidation of local molecular signalling pathways on complex biological surfaces.
Objectives: MSI will be employed as a high resolution in situ technique to identify new biomarkers.
Expected Results: New and novel insights into pathways involved in tumour immunology.
Planned secondments: to PERC to learn about product development (1 month), to LUMC to correlate MSIwith conventional histology (1 month), to TUD to integrate and map out the immune regulatory pathways derived from MSI (1 month).
ESR 5
Employer: TUD (Technical University of Delft)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP2
Map out specific gene signatures to predict for disease progression in HUMANS and utilising this as the basis to formulating different immunomodulation strategies (Activity type: Research).
Task details WP2.1: Utilisation of preclinical data from WP1 and determine those pathways that predict for disease progression in humans using t-SNE to visualise high-dimensional datasets.
Objectives: To identify those immune genes that are of more relevance in humans. Gene profiles from whole blood samples derived from surgery patients will be compared with preclinical immune gene profiles. The gene expression data from our study will be correlated to similar profiles identified from databases such has the Cancer Genome Atlas.
Expected Results: A protocol to reveal sets of genes derived from peripheral whole blood that will identify with certain tumour types (ovarian, breast, colorectal).
Planned secondments: to MAAS to identify new gene pathways (2 months), to JENA to learn about product development (2 months).
Employer: TUD (Technical University of Delft)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP2
Map out specific gene signatures to predict for disease progression in HUMANS and utilising this as the basis to formulating different immunomodulation strategies (Activity type: Research).
Task details WP2.1: Utilisation of preclinical data from WP1 and determine those pathways that predict for disease progression in humans using t-SNE to visualise high-dimensional datasets.
Objectives: To identify those immune genes that are of more relevance in humans. Gene profiles from whole blood samples derived from surgery patients will be compared with preclinical immune gene profiles. The gene expression data from our study will be correlated to similar profiles identified from databases such has the Cancer Genome Atlas.
Expected Results: A protocol to reveal sets of genes derived from peripheral whole blood that will identify with certain tumour types (ovarian, breast, colorectal).
Planned secondments: to MAAS to identify new gene pathways (2 months), to JENA to learn about product development (2 months).
ESR 6
Employer: TECO (TECOBiosciences GmbH)
PhD Reg.: MAAS (University of Maastricht)
Duration: 36 months
Work Package WP2
Map out specific gene signatures to predict for disease progression in HUMANS and utilising this as the basis to formulating different immunomodulation strategies (Activity type: Research).
Task details WP2.2: Unravel pathways of the myeloid and lymphoid lineages in ovarian, breast and colorectal cancer.
Objectives: To highlight aberrant pathways which will then be mapped to known annotations and relevant immune gene profiles.
Expected Results: A protocol that can predict for disease progression.
Planned secondment(s): to PERC to validate these pathways using molecular imaging techniques on in vivo syngeneic mice models (9 months), to LUMC to make in vivo gene reporter assays (3 months), to MAAS for high resolution MSI and PhD registration (3 months).
Employer: TECO (TECOBiosciences GmbH)
PhD Reg.: MAAS (University of Maastricht)
Duration: 36 months
Work Package WP2
Map out specific gene signatures to predict for disease progression in HUMANS and utilising this as the basis to formulating different immunomodulation strategies (Activity type: Research).
Task details WP2.2: Unravel pathways of the myeloid and lymphoid lineages in ovarian, breast and colorectal cancer.
Objectives: To highlight aberrant pathways which will then be mapped to known annotations and relevant immune gene profiles.
Expected Results: A protocol that can predict for disease progression.
Planned secondment(s): to PERC to validate these pathways using molecular imaging techniques on in vivo syngeneic mice models (9 months), to LUMC to make in vivo gene reporter assays (3 months), to MAAS for high resolution MSI and PhD registration (3 months).
ESR 7
Employer: JENA (Jenacell)
PhD Reg.: UVA (University of Amsterdam)
Duration: 36 months
Work Package: WP2
Map out specific gene signatures to predict for disease progression in HUMANS and utilising this as the basis to formulating different immunomodulation strategies (Activity type: Research).
Task details: WP2.3: Development of human immune gene profiling panels that can predict for outcome.
Objectives: Assay development and validation.
Expected Results: Assays of immune gene profiles that can used for immunotherapeutic monitoring and tracking disease progression.
Planned secondments: to PERC to test out the immune regulatory gene signatures on in vivo syngeneic mice models (6 months), to LUMC to test out the assays on cell lines (6 months), to UVA for analysis on UCPNs and PhD registration (3 months).
Employer: JENA (Jenacell)
PhD Reg.: UVA (University of Amsterdam)
Duration: 36 months
Work Package: WP2
Map out specific gene signatures to predict for disease progression in HUMANS and utilising this as the basis to formulating different immunomodulation strategies (Activity type: Research).
Task details: WP2.3: Development of human immune gene profiling panels that can predict for outcome.
Objectives: Assay development and validation.
Expected Results: Assays of immune gene profiles that can used for immunotherapeutic monitoring and tracking disease progression.
Planned secondments: to PERC to test out the immune regulatory gene signatures on in vivo syngeneic mice models (6 months), to LUMC to test out the assays on cell lines (6 months), to UVA for analysis on UCPNs and PhD registration (3 months).
ESR 8
Employer: MEDRES (Medres Köln)
PhD Reg.: LUMC (Leiden University Medical Center)
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.1: fMRI and optical imaging of macrophage M1 / M2 polarisation.
Objectives: To label MQs with 19F encapsulated PLGA NPs.
Expected Results: In vivo tracking and differentiation of macrophage M1 / M2 polarisation.
Planned secondments: to LUMC to integrate optical and MRI moieties onto biomaterial carriers (2 months), to US to develop multimodality labelling and imaging of MQs (2 months).
Employer: MEDRES (Medres Köln)
PhD Reg.: LUMC (Leiden University Medical Center)
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.1: fMRI and optical imaging of macrophage M1 / M2 polarisation.
Objectives: To label MQs with 19F encapsulated PLGA NPs.
Expected Results: In vivo tracking and differentiation of macrophage M1 / M2 polarisation.
Planned secondments: to LUMC to integrate optical and MRI moieties onto biomaterial carriers (2 months), to US to develop multimodality labelling and imaging of MQs (2 months).
ESR 9
Employer: UB (University of Bergen)
PhD Reg.: UB (University of Bergen)
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.2: Development of PDX of ovarian cancer in humanised mouse models for immunotherapy testing.
Objectives: To further develop our in-house orthotopic surgical ovarian cancer PDX model (from WP1.1) for both surgical intervention and adjuvant immunotherapy. The immuno-deficient host and engraftment conditions in the NSG mouse will be determined for optimum immune reconstitution and engrafted withPBMC or CD34+ human stem cells.
Expected Results: Circulating CD34+ or T-cell populations (activated CD4+, CD8+ and regulatory T cells) will be isolated from patient blood and ascetic fluid employed to regenerate components of the donors immune system to provide an immunocompetent model for the studies of WP4.
Planned secondment: to LUMC to test out the PDX model (2 months), to MAAS to identify extent of human immune gene engraftment (1 month), to HH for the PDX (4 months).
Employer: UB (University of Bergen)
PhD Reg.: UB (University of Bergen)
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.2: Development of PDX of ovarian cancer in humanised mouse models for immunotherapy testing.
Objectives: To further develop our in-house orthotopic surgical ovarian cancer PDX model (from WP1.1) for both surgical intervention and adjuvant immunotherapy. The immuno-deficient host and engraftment conditions in the NSG mouse will be determined for optimum immune reconstitution and engrafted withPBMC or CD34+ human stem cells.
Expected Results: Circulating CD34+ or T-cell populations (activated CD4+, CD8+ and regulatory T cells) will be isolated from patient blood and ascetic fluid employed to regenerate components of the donors immune system to provide an immunocompetent model for the studies of WP4.
Planned secondment: to LUMC to test out the PDX model (2 months), to MAAS to identify extent of human immune gene engraftment (1 month), to HH for the PDX (4 months).
ESR 10
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 12 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.3: New multi-coloured luciferase assays to measure NF-κB response.
Objectives: To develop an assay to measure the NF-κB response in T cells or tumour cell lines.
Expected Results: Established tumour cell lines carrying dual (red / green) luciferase constructs and T-cells transduced with a construct where one luciferase is expressed constitutively and the other is under the control of the NF-κB promotor.
Planned secondments: to JENA to understand about assay development processes (1 month).
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 12 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.3: New multi-coloured luciferase assays to measure NF-κB response.
Objectives: To develop an assay to measure the NF-κB response in T cells or tumour cell lines.
Expected Results: Established tumour cell lines carrying dual (red / green) luciferase constructs and T-cells transduced with a construct where one luciferase is expressed constitutively and the other is under the control of the NF-κB promotor.
Planned secondments: to JENA to understand about assay development processes (1 month).
ESR 11
Employer: PERC (Percuros, Leiden)
PhD Reg.: LUMC (Leiden University Medical Center)
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.4: New multi-coloured luciferase in vivo assays to measure immune function.
Objectives: To provide in vivo multi-coloured tracking of T-cells and MQs.
Expected Results: Triple coloured (red / green /blue) luciferase labelled cells: M1 MQs /M2 MQs/tumour and naive T-cells/ active t-cells/tumour.
Planned secondments: to US to co-develop labelling tools (2 months), to LUMC to develop the constructs (4 months).
Employer: PERC (Percuros, Leiden)
PhD Reg.: LUMC (Leiden University Medical Center)
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.4: New multi-coloured luciferase in vivo assays to measure immune function.
Objectives: To provide in vivo multi-coloured tracking of T-cells and MQs.
Expected Results: Triple coloured (red / green /blue) luciferase labelled cells: M1 MQs /M2 MQs/tumour and naive T-cells/ active t-cells/tumour.
Planned secondments: to US to co-develop labelling tools (2 months), to LUMC to develop the constructs (4 months).
ESR 12
Employer: UC (University of Camerino)
PhD Reg.: UC
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.5: Development of biodegradable NPs as vaccine adjuvants and delivery systems.
Objectives: To optimise the PLGA platform by modification of hydrophobic / hydrophilic properties, charge density, biodegradation rate and molecular weight.
Expected Results: Optimised PLGA NPs made functional as a vaccine adjuvant.
Planned secondments: to PERC to work together on PLGA structural modifications (2 months), to UVA to develop the UCNPs (2 months), to EPFL to optimise the bioorthogonal labelling (1 month).
Employer: UC (University of Camerino)
PhD Reg.: UC
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.5: Development of biodegradable NPs as vaccine adjuvants and delivery systems.
Objectives: To optimise the PLGA platform by modification of hydrophobic / hydrophilic properties, charge density, biodegradation rate and molecular weight.
Expected Results: Optimised PLGA NPs made functional as a vaccine adjuvant.
Planned secondments: to PERC to work together on PLGA structural modifications (2 months), to UVA to develop the UCNPs (2 months), to EPFL to optimise the bioorthogonal labelling (1 month).
ESR 13
Employer: UVA (University of Amsterdam)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.6: Development of UCNPs with a photon-switchable dual function for both MRI and/or optical imaging and immunotherapy.
Objectives: To optimise the rare earth-doping of UCNPs to make them functional for imaging at depth as well as cross-compatible to incorporate immune components.
Expected Results: Targeted UCNPs optimised to perform immunotherapy and MRI and/or optical imaging.
Planned secondments: to PERC to write a business plan (1 months), to EPFL to optimise labelling (2 months), to MEDRES to incorporate 19F into the UCNPs (1 month).
Employer: UVA (University of Amsterdam)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.6: Development of UCNPs with a photon-switchable dual function for both MRI and/or optical imaging and immunotherapy.
Objectives: To optimise the rare earth-doping of UCNPs to make them functional for imaging at depth as well as cross-compatible to incorporate immune components.
Expected Results: Targeted UCNPs optimised to perform immunotherapy and MRI and/or optical imaging.
Planned secondments: to PERC to write a business plan (1 months), to EPFL to optimise labelling (2 months), to MEDRES to incorporate 19F into the UCNPs (1 month).
ESR 14
Employer: EPFL (Ecole Polytechnique Fédérale de Lausanne)
PhD Reg.: EPFL
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.7: Targeting of biomaterials (PLGA and UCNPs) to generate responses tailored for cancer intervention after surgery.
Objectives: To develop targeting chemistry for the NPs or MPs and investigate the use of bioorthogonal chemistry where a chemical reaction can occur inside of living systems without interfering with native biochemical processes.
Expected Results: These are natural endogenous reactions, which lack immunogenicity because of the extremely small size of the reagents and their complete absence in natural system. We will utilise this ‘click-chemistry’ for cell labelling and tracking strategy based on metabolic glycoengineering. Unnatural sialic acids with azide groups would be artificially induced on the surface of target cells by glycoengineering and then effectively tracked by dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5) in vivo using bioorthogonal click chemistry.
Planned secondments: to LUMC to work on different biomaterial-based particles (4 months), to UVA to work on UCNPs as a vehicle (1 month).
Employer: EPFL (Ecole Polytechnique Fédérale de Lausanne)
PhD Reg.: EPFL
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.7: Targeting of biomaterials (PLGA and UCNPs) to generate responses tailored for cancer intervention after surgery.
Objectives: To develop targeting chemistry for the NPs or MPs and investigate the use of bioorthogonal chemistry where a chemical reaction can occur inside of living systems without interfering with native biochemical processes.
Expected Results: These are natural endogenous reactions, which lack immunogenicity because of the extremely small size of the reagents and their complete absence in natural system. We will utilise this ‘click-chemistry’ for cell labelling and tracking strategy based on metabolic glycoengineering. Unnatural sialic acids with azide groups would be artificially induced on the surface of target cells by glycoengineering and then effectively tracked by dibenzylcyclooctyne-conjugated Cy5 (DBCO-Cy5) in vivo using bioorthogonal click chemistry.
Planned secondments: to LUMC to work on different biomaterial-based particles (4 months), to UVA to work on UCNPs as a vehicle (1 month).
ESR 15
Employer: US (University of Sheffield)
PhD Reg.: US
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.8: Phenotyping of circulating monocytes and MQs in metastasis after surgery.
Objectives: To monitorM1/M2 phenotypic switching (green/red luciferase) in circulating monocytes and TAMs, before and after image-guided surgery in mice, and throughout the time course of adjuvant chemotherapy.
Expected Results: Onset of an M2 phenotype will be optically monitored and correlated with the production of immunosuppressive factors by TAMs.
Planned secondments: to PERC to test and optimise the transgenic mouse model for dual coloured readouts (2 months), to LUMC for the in vivo measurements (4 months).
Employer: US (University of Sheffield)
PhD Reg.: US
Duration: 36 months
Work Package: WP3
Development and testing of preclinical models and biodegradable materials for immunotherapy (Activity type: Research)
Task details: WP3.8: Phenotyping of circulating monocytes and MQs in metastasis after surgery.
Objectives: To monitorM1/M2 phenotypic switching (green/red luciferase) in circulating monocytes and TAMs, before and after image-guided surgery in mice, and throughout the time course of adjuvant chemotherapy.
Expected Results: Onset of an M2 phenotype will be optically monitored and correlated with the production of immunosuppressive factors by TAMs.
Planned secondments: to PERC to test and optimise the transgenic mouse model for dual coloured readouts (2 months), to LUMC for the in vivo measurements (4 months).
ESR 16
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 12 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.1: NP -based vaccine and checkpoint blockade combination immunotherapy.
Objectives: To combine a checkpoint blocker and a SLP vaccine as a strategy for systemic immunotherapy.
Expected Results: Improved outcome and survival with dual combination SLP vaccine and a single checkpoint blocker encapsulated in a NP.
Planned secondments: to TECO to refine the best combination (1 months), to UB to work with the ovarian cancer model (1 month).
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 12 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.1: NP -based vaccine and checkpoint blockade combination immunotherapy.
Objectives: To combine a checkpoint blocker and a SLP vaccine as a strategy for systemic immunotherapy.
Expected Results: Improved outcome and survival with dual combination SLP vaccine and a single checkpoint blocker encapsulated in a NP.
Planned secondments: to TECO to refine the best combination (1 months), to UB to work with the ovarian cancer model (1 month).
ESR 17
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: LUMC
Duration: 36 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.2: A NP-based library of defined immune regulatory components for immunotherapy.
Objectives: To combine and test different immune regulatory reagents which are incorporated inside NPs for systemic administration. Longitudinal immune regulatory gene profiling studies to monitor progress of therapy.
Expected Results: Improved outcome and survival with select immunotherapeutic combinations.
Planned secondments: to TECO to refine the best combination (1 month), to UB to work with the ovarian cancer model (1 month).
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: LUMC
Duration: 36 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.2: A NP-based library of defined immune regulatory components for immunotherapy.
Objectives: To combine and test different immune regulatory reagents which are incorporated inside NPs for systemic administration. Longitudinal immune regulatory gene profiling studies to monitor progress of therapy.
Expected Results: Improved outcome and survival with select immunotherapeutic combinations.
Planned secondments: to TECO to refine the best combination (1 month), to UB to work with the ovarian cancer model (1 month).
ESR 18
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 12 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.3: A MP-based library of defined immune regulatory components for immunotherapy for local delivery at the wound site after surgery.
Development and optimization (PLGA platform by modification of hydrophobic/hydrophilic properties, charge density, biodegradation rate and molecular weight) of biodegradable PLGA materials for immunotherapy and vaccine adjuvant. including i) preparation and optimization of PLGA NP-based library of distinct components (checkpoint blocker Abs) for immunotherapy, ii) to prepare a PLGA nanoparticles containing 19F encapsulated for labelling MQs and iii) targeting of biomaterials (PLGA) to generate responses tailored for cancer immunotherapy.
Objectives: To combine and test different immune regulatory reagents which are incorporated inside MPs for systemic administration at the wound site after surgery. Longitudinal immune regulatory gene profiling studies to monitor progress of therapy.
Expected Results: Improved outcome and survival with select immunotherapeutic combinations.
Planned secondments: to TECO to refine the best combination (1 month), to UB to work with the PDXmodels (1 month), to UC to optimise the MP design (1 month).
Ideal candidate: We are looking for an enthusiastic candidate with a MSc degree in bio-pharmaceutical, pharmaceutical, biomedical science, immunology, oncology, or related disciplines with a strong background in nanodelivery system and preferable with art.9 certificate.
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 12 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.3: A MP-based library of defined immune regulatory components for immunotherapy for local delivery at the wound site after surgery.
Development and optimization (PLGA platform by modification of hydrophobic/hydrophilic properties, charge density, biodegradation rate and molecular weight) of biodegradable PLGA materials for immunotherapy and vaccine adjuvant. including i) preparation and optimization of PLGA NP-based library of distinct components (checkpoint blocker Abs) for immunotherapy, ii) to prepare a PLGA nanoparticles containing 19F encapsulated for labelling MQs and iii) targeting of biomaterials (PLGA) to generate responses tailored for cancer immunotherapy.
Objectives: To combine and test different immune regulatory reagents which are incorporated inside MPs for systemic administration at the wound site after surgery. Longitudinal immune regulatory gene profiling studies to monitor progress of therapy.
Expected Results: Improved outcome and survival with select immunotherapeutic combinations.
Planned secondments: to TECO to refine the best combination (1 month), to UB to work with the PDXmodels (1 month), to UC to optimise the MP design (1 month).
Ideal candidate: We are looking for an enthusiastic candidate with a MSc degree in bio-pharmaceutical, pharmaceutical, biomedical science, immunology, oncology, or related disciplines with a strong background in nanodelivery system and preferable with art.9 certificate.
ESR 19
Employer: US (University of Sheffield)
PhD Reg.: LUMC (Leiden University Medical Center)
Duration: 36 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.4: Phenotyping of circulating monocytes and MQs in metastasis after surgery.
Objectives: Test in vitro (using a 3 D spheroid system) and in vivo the ability of PLGA NPs to target an oncolytic virus containing CMV-eGFP reporter to circulating monocytes and TAMs (and check specificity of this targeting).
Expected Results: NP-based oncolytic virus delivery into monocytes in circulation (in vivo) without the need for ex vivo manipulation of monocyte-derived MQs. Effect of this therapy on tumour suppression will also be assessed.
Planned secondments: to PERC to look at specificity of the NPs to their targets (2 months), to LUMC to work on incorporating the oncolytic virus into NPs (4 months).
Employer: US (University of Sheffield)
PhD Reg.: LUMC (Leiden University Medical Center)
Duration: 36 months
Work Package: WP4
Postoperative (adjuvant) biomaterial-based delivery of therapeutics and subsequent outcome studies in mice (Activity type: Research)
Task details: WP4.4: Phenotyping of circulating monocytes and MQs in metastasis after surgery.
Objectives: Test in vitro (using a 3 D spheroid system) and in vivo the ability of PLGA NPs to target an oncolytic virus containing CMV-eGFP reporter to circulating monocytes and TAMs (and check specificity of this targeting).
Expected Results: NP-based oncolytic virus delivery into monocytes in circulation (in vivo) without the need for ex vivo manipulation of monocyte-derived MQs. Effect of this therapy on tumour suppression will also be assessed.
Planned secondments: to PERC to look at specificity of the NPs to their targets (2 months), to LUMC to work on incorporating the oncolytic virus into NPs (4 months).
ESR 20
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP5
Combination adjuvant immunotherapy in canines of the most promising combinations from WP4 (Activity type: Research)
Task details: WP5.1: IGS and combination adjuvant immunotherapy in canines of the most promising combinations.
Objectives: The best combined biomaterial-based immunotherapy format from the mouse studies (of WP4) to be tested in canines.
Expected Results: Improved outcome and survival rates in the canine studies. To have in place a protocol that can be translated from canines and eventually be implemented for a first-in-man study.
Planned secondments: to TECO to draw up a development plan for eventual phase 0 (first-in-man) study (1 month), to LUMC to optimise the image-guided surgery technique (4 months), to UB to study the ovarian cancer model for surgery (1 month).
Employer: LUMC (Leiden University Medical Center)
PhD Reg.: n. a.
Duration: 18 months
Work Package: WP5
Combination adjuvant immunotherapy in canines of the most promising combinations from WP4 (Activity type: Research)
Task details: WP5.1: IGS and combination adjuvant immunotherapy in canines of the most promising combinations.
Objectives: The best combined biomaterial-based immunotherapy format from the mouse studies (of WP4) to be tested in canines.
Expected Results: Improved outcome and survival rates in the canine studies. To have in place a protocol that can be translated from canines and eventually be implemented for a first-in-man study.
Planned secondments: to TECO to draw up a development plan for eventual phase 0 (first-in-man) study (1 month), to LUMC to optimise the image-guided surgery technique (4 months), to UB to study the ovarian cancer model for surgery (1 month).
For more details about the specific work packages please visit www.ispic.eu.
MSCA-ITN eligibility criteria
There are strict eligibility requirements for the ESR PhD positions in MSCA-ITN. Please ensure that you qualify before applying, as ineligible candidates cannot be considered.
• Applicants should not have resided or performed their main activity (work, studies, etc.) in the country of the host institution for more than 12 months in the 3 year period immediately prior to the start date of the PhD research.
• Applicants for the ESR PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining the degree which would formally entitle to embark on a doctorate.
• Applicants should not have resided or performed their main activity (work, studies, etc.) in the country of the host institution for more than 12 months in the 3 year period immediately prior to the start date of the PhD research.
• Applicants for the ESR PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining the degree which would formally entitle to embark on a doctorate.
The candidate should be highly motivated and able to work independently, as well as in a team. Knowledge or affinity to cancer biology, molecular imaging, and nanodelivery system is highly welcome. The candidate must have excellent oral and written communication skills and aptitude for interacting with other researchers.
MSCA-ITN offers attractive salary and working conditions. A unique feature of MSCA-ITN is that during the PhD research, ESR PhD students will be given the opportunity to perform at least two secondments of about 3 months each at the facilities of other consortium members. ESR PhD students will benefit from a dedicated training program in the various fields of expertise of the consortium partners. Salary is complemented with a mobility allowance.
For more information on MSCA-ITN, visit
http://ec.europa.eu/research/mariecurieactions/about-msca/actions/itn/index_en.htm
For more information on MSCA-ITN, visit
http://ec.europa.eu/research/mariecurieactions/about-msca/actions/itn/index_en.htm
Application
To apply for one of this positions please send the following information to jobs@ispic.eu:
• your complete CV,
• motivation letter,
• copies of University Master certificates or equivalents and
• contact details of two referees, who can provide a letter of recommendation.
Please state the vacancy reference including the specific number (for example "ISPIC ESR #", # = 1…20) in the subject line. After eligibility screening, your application will be forwarded to the consortium members for further evaluation….
• your complete CV,
• motivation letter,
• copies of University Master certificates or equivalents and
• contact details of two referees, who can provide a letter of recommendation.
Please state the vacancy reference including the specific number (for example "ISPIC ESR #", # = 1…20) in the subject line. After eligibility screening, your application will be forwarded to the consortium members for further evaluation….
Don't forget to mention Naturejobs when applying.
No comments:
Post a Comment