This 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 - Contribute to the acquisition of knowledge and new insights within the context of the department’s research program.
- Design and perform scientific research.
- Write scientific publications and present research data at scientific meetings and conferences.
- Work in a team with clinical and non-clinical PhD students and scientists.
- Discuss, plan and perform research in a stimulating environment.
- Work in an international research group.