Interested in Immunology and Immunotherapy, join our team and exciting translational research program!This project focuses on the preclinical exploration of novel immunotherapies against Acute Myeloid Leukemia (AML). Every year, approximately 500 new patients are diagnosed with AML. In 30% of these patients the prognosis is poor due to unfavorable characteristics of the leukemia cells. Allogeneic stem cell transplantation (alloSCT) can be a curative treatment for AML patients. However, relapse post-alloSCT remains a major problem. This emphasizes the need for more effective treatment options to maximally reduce tumor load prior to alloSCT and improve the window of opportunity for graft-versus-leukemia immunity.
To achieve these goals, hypomethylating agents (HMA), such as azacitidine and decitabine, are highly attractive because these agents are well-tolerated and exert direct anti-proliferative and pro-apoptotic effects on tumor cells. Interestingly, HMA can also modulate tumor immunogenicity and enhance T cell and natural killer (NK) cell responses, thereby promoting anti-tumor immunity. Recently in an explorative study, we observed improved relapse-free survival and enhanced frequencies of tumor-reactive T cells in patients treated with decitabine prior to alloSCT. Yet, still many poor-risk AML patients relapsed.
To prevent disease relapse and eventually cure patients it is important to provide extra boost of the tumor-reactive immune responses. Because of decitabine's immune promoting effects, combination treatment with cellular immunotherapy is a unique strategy with strong potential to establish long-lasting tumor control, without causing severe toxicity. In this regard, vaccination with natural dendritic cell (DC) subsets holds great potential, as DC are the key orchestrators of anti-tumor immunity.
Recently, we developed an innovative ex vivo culture protocol to generate high numbers of myeloid and plasmacytoid DC from hematopoietic stem and progenitor cells (HSPC), with exceptional T and NK cell stimulatory potential. This project aims at investigating the effects of decitabine exposure on tumor immunogenicity, as well as on priming of tumor-reactive T and NK cell responses in AML patients. Furthermore, HSPC-derived myeloid and plasmacytoid DC vaccines will be further developed as adjuvant immunotherapy for boosting of decitabine-primed tumor-reactive T and NK cell responses. We anticipate that these studies will provide rationale for combined immunomodulation by decitabine and DC-based immunotherapy to boost graft-versus-leukemia immunity, and establish long-lasting disease control.
For this project we are looking for an enthusiastic research technician, who in close collaboration with PhD students will perform independent experiments, document and report research results and contribute to scientific publications.
Tasks and responsibilities
- The technician contributes to the development of new knowledge within the context of the department's research program.
- Isolation and cryopreservation of mononuclear cells from patient' blood and/or bone marrow.
- Isolation of T and NK cells from blood and bone marrow for functional assays.
- Culture of myeloid and plasmacytoid dendritic cells for functional assays.
- Independent performance of cellular immunological assays and multi-color flow cytometry assays.
- Presentation and discussion of research data (written reports, team meetings).
- Translation of research findings to methods and protocols.