PhD candidate ‘Engineering stem cell-derived NK cells with multi-antigen targeting chimeric antigen receptors and transpresented IL15 for immunotherapy of acute myeloid leukemia’
Offer DescriptionThis KiKa-funded project focuses on establishing a novel cellular immune therapy for acute myeloid leukemia (AML). Interested in Cancer Immunology and Immunotherapy and pursuing a PhD career? Join our exciting translational research group!Currently, for both childhood and adult AML the 5-year overall survival is poor, and patients do not survive due treatment-related toxicity or relapse. Therefore, potent adjuvant therapies are needed to improve outcome with limited treatment-related side effects.Adjuvant allogeneic natural killer (NK)-based immunotherapy is a promising and well-tolerated therapeutic approach for AML, exerting encouraging anti-leukemic activity. However, further enhancement of its therapeutic efficacy is needed to achieve more and longer-lasting clinical responses. We therefore established a GMP-compliant culture system to manufacture off-the-shelf allogeneic Natural Killer (NK) cell products from umbilical cord blood (UCB)-derived CD34+ hematopoietic progenitor cells (HPC). In non-clinical studies this HPC-NK cell product (devoid of allogeneic T cell-contamination) exerts potent anti-AML reactivity.Our clinical studies showed that nonengineered HPC-NK cells can be safely administered to AML patients with transient anti-leukemia reactivity. To further increase clinical efficacy, we propose to engineer HPC-NK cells with multiple chimeric antigen receptors (CARs) to maximize AML-directed cytotoxicity, combined with transpresentation of IL15 tethered with IL15Rα (tIL15) to improve CAR-NK cell expansion and activity. The aim of this project is to establish an off-the-shelf CAR-HPC-NK cell product combined with tIL15, for immunotherapy of (childhood) AML patients with refractory disease. For this, we will apply viral transduction with (single or multi-antigenic) CARs, combined with tIL15 in our GMP-compliant HPC-NK production protocol. Furthermore, we will evaluate anti-AML effects and off-tumor toxicity in vitro and in preclinical mouse models.This project aims to deliver a potent off-the-shelf CAR-tIL15 HPC-NK cell product with improved expansion, anti-AML reactivity and limited on-target off-tumor toxicity as an effective on-demand adjuvant immunotherapy, to prolong relapse-free survival and potentially cure (childhood) AML patients.For this project, we are looking for an ambitious PhD student. This four-year project should culminate in a PhD thesis. You will participate in the Radboudumc Graduate School and Radboud Research Program “Treatment Improvements for Severe Hematological Diseases”.Tasks and responsibilities
Where to apply WebsiteRequirementsSpecific RequirementsOur ideal candidate has a Master degree in (Medical) Biology, Biomedical sciences, Molecular Mechanisms of Disease, Molecular life sciences, Medicine or similar. You have the enthusiasm and ambition to succeed in translational academic research. You are assertive, ambitious and a team-player. Further, you have well-developed social skills directed to work in a team, and excellent interpersonal and communicative skills.You are able to independently plan and carry out highly complex immunological experiments. In addition, you are highly motivated to work in an interdisciplinary environment using state-of-the-art technologies. You have affinity with cell culture (of primary immune cells), molecular techniques (e.g. cloning and/or CRISPR), viral transduction, (high dimensional) flow cytometry, cellular immunology assays and data analyses. Animal experimentation is no objection to you and you have an Article 9 Certificate of the Experiments on Animals Act.Additional InformationBenefitsAt Radboud university medical center, you build on your future. We are committed to providing the best care, education, and research. And we are true to our word, because we help you develop and seize opportunities and give you the room to grow. As an employer, we believe that employees should feel vital and happy at work in all stages of life. We are also committed to creating a healthy and safe working environment. Our employment conditions contribute to that. What we offer:
Selection processAny questions? Or wondering what it is like to work at Radboudumc? Then call, send a message or email to professor , through (024) 361 97 53. Use the Apply button to submit your application.Additional commentsAny questions? Or wondering what it is like to work at Radboudumc? Then call, send a message or email to professor , through (024) 361 97 53. Use the Apply button to submit your application. Website for additional job detailsWork Location(s)Number of offers available 1 Company/Institute Radboudumc Country Netherlands City Nijmegen Postal Code 6525 GA Street Geert Grooteplein-Zuid 10 GeofieldContact CityNijmegen WebsiteStreetGeert Grooteplein-Zuid 10 Postal Code6525 GASTATUS: EXPIREDShare this page
Nijmegen, Gelderland
Sun, 21 Jul 2024 06:33:49 GMT
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