Killer Cells © CiMaas

The Maastricht University Medical Center (MUMC+) receives a grant for research into Killer Cells and Breast Cancer. The subsidy (1.48 million euros) was provided by KWF, which is the secretary for the national initiative LSH-TKI (Life Science Health, Top Consortia for Knowledge and Innovation), from Health-Holland.

Within the MUMC+, research has been conducted for several years into the possible beneficial effects of immunotherapy with killer cells in breast cancer, the organization says in a press release. In cell culture systems and also in laboratory animals it has been possible to show that these killer cells – a type of white blood cells – can have an anti-cancer effect. Different strategies have been developed to make Killer cells resistant to the inhibitory influence of the tumor microenvironment.

In addition, a spin-off of the MUMC+ (CiMaas) will further develop the killer cells so that they can actually be tested in patients with metastatic breast cancer, based on the hopefully favorable results resulting from this research. “This process has now been developed to such an extent that we expect to be able to make definitive plans in 2022 for testing these cells in patients with multiple myeloma and/or acute leukemia.”

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    This is important because this tumor environment is a bottleneck for many types of anti-cancer therapy. Research that was largely realized by donors in the region, via the Cancer Research Fund Limburg. In the next phase, together with the University of Utrecht, MUMC+ will further investigate the possibilities of killer cells in metastatic breast cancer.

    CiMaas

    The KWF report “Cell and gene therapy to oncological clinical practice” wrote various recommendations to advance the field including developing start-ups. Already in 2015, the University of Maastricht started a spin-off called CiMaas, which since 2019 owns a Class B-cleanroom to produce ATMPs. CiMaas is capable to produce NK cells for the preclinical research described in this project. During the project, CiMaas will develop a fully closed, GMP grade system to render this ATMP as cost-efficient as possible for clinical use. The set-up of the consortium will ensure the inclusion of both the technology for standardized GMP grade NK cells, as well as the needed preclinical knowledge of the effect of (CAR-)NK cells in (lobular) breast cancer. As such, the step to clinical trials can be made without further delay. CiMaas will provide the required infrastructure for others that intend to use NK cells in (clinical) studies.

    Project

    Natural Killer (NK) cells are effector cells of our immune system that can kill malignant cells. They are effective in patients with hematological malignancies. MUMC+ has demonstrated the efficacy of NK cells, both in models for M. Myeloma and breast cancer. “In this consortium we further explore the role of NK cells in metastatic (lobular) breast cancer, bringing groups together to combine knowledge on NK cells and preclinical breast cancer models. Survival is poor if the disease is metastasized. Treatment is an unmet medical need for this situation. The anti-tumor effect of NK cells will be studied in mouse (PDX) models and human patient-derived tumor organoid (PDO) models. In the project, we will also develop a Chimeric Antigen Receptor (CAR)-NK cell with a tumor-specific anti-Mucin-1 and Her2 antibody fragment to optimize NK cell effectivity. The PDX and PDO models are expected to be predictive for the clinical effects of NK and CAR-NK cells. A limitation of cell therapy is the high complexity – classified as ATMP – since strict regulations are in place for the production of these cells.”

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