This project provides future-oriented translational research training designed to bridge the gap between basic research and applied development of new cell-based therapeutic products by the biotech industry and their clinical use for incurable diseases. This is done on the example of activated/genetically manipulated natural killer (NK) cells, which are classified as Advanced Therapy Medicinal Products ("ATMPs"), and their use in the treatment of cancer refractory to classical therapies. For this we combine experts in NK cell biology supported by bioinformatics, clinical groups pioneering NK cell therapies and biotech companies with NK cell-based portfolios. A student exchange will ensure training in basic, clinical and industrial sectors. The network-wide training modules organized in summer/winter schools include immunotechnology, business management and intellectual property rights. This will train competences important to translate research findings to personalized medicine.

In the research part we will build on information obtained by our clinical partners in previous and ongoing clinical trials of NK cell-based therapies. We will focus on possibilities to improve and amplify anti-tumor reactivity of NK cells. This will include selection and specific modification of NK cells as well as modulation of NK receptor/ligand interactions to achieve appropriate anti-tumor reactivity. The first part will comprise i) improved donor/recipient combination and NK subsets for therapy and ii) the modification of NK cells by chimeric antigen receptors ("CAR") and bi/trispecifc antibody reagents to cross-link the cells to their tumor targets. The second part will investigate the possibilities to fortify NK cell reactivity by i) blocking the ligand interactions of inhibitory receptors ("checkpoint inhibitors") and ii) defining unknown ligands of activating NK receptors on tumor cells and their potential for eliciting NK cell cytotoxicity. In the third part appropriate procedures and modified NK products in their best combination will be taken into an evaluation/development pipeline comprising i) testing in humanized mouse models, ii) development of a large-scale GMP-compliant manufacturing process and iii) design of a clinical trial protocol. Thus the project should provide a basis for future manufacturing of NK cell-based therapeutic products by our company partners and their evaluation in clinical trials by the clinical partners.


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