Stageplek Celtherapie

Academic Multiple Myeloma CAR-T therapy development

The Hematology Department of the Amsterdam University Medical Center (location VUmc) is one of the largest Dutch treatment centers for patients suffering from hematological cancers (leukemia, lymphoma, and myeloma). The Department also conducts research into better cancer treatment, with a focus on advanced cellular immune therapy. The Department develops innovative CAR-T cell therapy and tests these in clinical trials.

Cancer is the second cause of premature death world-wide. Classic cancer treatment, focused on killing or removing cancer cells, consistis of chemotherapy, surgery, radiation, or combinations of these. While they can be very effective and in many cases are currently the standard treatment, they are all susceptible to treatment resistance and tumor recurrence, and are hampered by severe, sometimes fatal side-effects. Recently, immunotherapy, which aims at restoring the patient‘s own immune system to recognize and destroy tumours, has shown great clinical success. One form of immunotherapy is adoptive cell transfer; the transfer of immune cells into the cancer patient.

Currently, these are usually T cells extracted from the patient, genetically modified and cultured in vitro and returned to the same patient by infusion, to act as a „living drug“. At present, the most successful genetic modification entails introduction of chimeric antigen receptors (CARs), chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor. CARs give T cells novel ability to target a specific antigen present on the cell surface of the tumor cells, and upon binding cause T cell proliferation and activate a cytotoxic T cell response to destroy these targeted cancer cells. CAR-T therapy has shown tremendous clinical promise, currently over 1,000 clinical trials are in progress, and six different CAR-T products have been approved for use as cancer therapy. Limitations to CAR-T therapy include toxicity to the patient, with serious (but transient) side effects, therapy escape by the tumor downregulating the expression of the targeted surface receptor, or the limited life span of the infused CAR-T cells. For this reason, CAR optimization is receiving intense attention from research groups worldwide. Our Department has recently published a dual CAR molecule that shows increased cytoxicity and increases the efficacy time of CAR-T cells. We are currently developing this molecule into a clinically effective cell therapy. The student project includes optimization of our CAR leads, optimization of current GMP T-cell culture process, testing of patient cells for clinical prioritization, and assay development. Techniques used are DNA cloning, cell culture, virus transduction, and various molecular biology and flow cytometry assays.

The student will by supervised by the team leader and supported by four junior scientists. The student will follow a jointly agreed project proposal, but also be expected to present ideas about current and future experiments and developments. Supervision and discussions will be daily, team meetings where work-in-progress will be presented  to all group members will be weekly. The student will also participate in weekly progress meetings and journal clubs for the whole Hematology Department.

Start: 01-07-2024 to 01-09-2024
Duration: 6 to 12 months
Level: Completed Bachelor in Biology, Biomedical Sciences, Medical Biology or Medicine

Intersse?

Mail dan naar: Dirk Geerts, PhD. Team Leader Fast Track

h.a.geerts@amsterdamumc.nl