Postdoc | Cancer Center Amsterdam

Your challenge
Immunotherapy holds great promise for the treatment of cancer. Several immunotherapeutic modalities have recently demonstrated their efficacy in multiple myeloma (a malignant disease of antibody-producing plasma cells), including (bispecific) antibodies. CD38 is highly expressed on myeloma cells, and plays a role in adhesion and migration. In our group we have provided the preclinical rationale for the treatment of multiple myeloma patients with therapeutic CD38-targeting antibodies (such as daratumumab). Although daratumumab is highly active in the treatment of multiple myeloma, most patients eventually relapse.

The goal of the current project is to extent this succesfull preclinical research by obtaining further insights into the mechanisms of action and modes of resistance towards daratumumab. Daratumumab has direct effects on the tumor, but also immune stimulatory activity. In addition, we have recently shown that in the process of trogocytosis, CD38-daratumumab complexes, but also tumor cell membrane fragments, are transferred from the myeloma cells to effector cells (granulocytes and monocytes). This results in marked reduction of CD38 on the tumor cell surface. Importantly, we demonstrated that trogocytosis also leads to decreased expression of adhesion molecules, which are critical for the tumor cells to interact with the protective bone marrow microenvironment. Impaired ability to interact with the environment may lead to reduced proliferation, impaired survival, and reduced protection against a wide variety of anti-cancer agents.

The specifc aim of the current project is to study the impact of daratumumab on the interaction of tumor cells and the bone marrow microenvironment (including immune cells) by the reduction in the expression of CD38 and other critical adhesion molecules present on the tumor cell surface.
The ultimate aim of this research is to further improve the treatment of myeloma patients with rationally designed combination therapy.

As a postdoctoral researcher your main tasks and responsibilities in this project are:

• To obtain novel insights into the mechanisms of action and modes of (immune) resistance towards the CD38-targeting antibody daratumumab in multiple myeloma;
• To examine the effect of the CD38-targeting antibody on interactions of tumor cells with the protective bone marrow micoenvironment;
• To design novel effective daratumumab-based combination strategies to improve the survival of myeloma patients.

We are looking for an enthusiastic, skilled, highly motivated postdoctoral researcher with:

• A PhD in oncology, immunology, genetics or closely related biomedical sciences;
• Candidates with expertise in molecular and cellular biology and primary cell cultures are encouraged to apply;
• Ability to effectively communicate scientific ideas, foster collaboration and demonstrable capability of independent thinking;
• Proficiency in English and a team player mentality.

Salary Scale 10: 2911 tot 4615 euro gross when employed full-time (depending on qualifications and experience).

In addition we offer:

• The base salary does not include allowances for irregular shifts, holiday pay (8%) and a year-end bonus (8.3%).
• Pension is accrued at the ABP. VUmc contributes a large part of the premium (70%).
• In addition to excellent accessibility by public transport, we reimburse 75% of your OV travel costs (commuting costs).

You will be temporarily employed for three years.

For more information about our employment conditions, please visit our website.

Working at Amsterdam UMC, VUmc location means working in an inspiring and professional environment where development is encouraged in every respect. We offer you ample opportunity for development, deepening and broadening, additional training and a place to grow!

The multiple myeloma Immunotherapy research group in the dept of Hematology at the Cancer Center Amsterdam, is seeking a highly motivated postdoctoral researcher for the ‘Evaluation of mechanisms of action and resistance of CD38-targeting antibodies in multiple myeloma’.

The department of Hematology of Amsterdam UMC, location VU University Medical Center (VUmc) is one of the biggest Hematological Centers in the Netherlands. The department is known for its high quality translational research aiming at developing and application of novel targeted and immunotherapeutic strategies toward the improvement of survival of patients with leukemia and multiple myeloma.