Presented by
Elisa Kieback

Nominated by
Max Delbrück Center

 

T-knife has developed a special mouse strain that generates efficient anti-cancer molecules. Using these molecules the immune system of a cancer patient can be reprogrammed to attack tumor cells and eliminate them just like they would attack a virus-infected cell. T-knife’s technology has the potential to revolutionise the treatment of solid tumors just as CAR-T have for leukemia. T cell therapy has been shown to lead to complete remission of tumors in patients refractory to virtually any other available therapy. This gives hope to be able to treat patients which have no options left.

T-knife’s humanized TCR (T cell receptor) mice carry the entire human TCR gene loci (about 2 MB of DNA) and recombine a broad repertoire of fully human TCRs – similarly to Ig-locus transgenic mice that produce fully human antibodies. This technology allows highly efficient “factory-like” generation and selection of TCRs for virtually any human tumor antigen. Since the mouse immune system is not tolerant to most human tumor antigens, T-knife’s TCRs are of optimal affinity. For tumor therapy, the TCRs are transferred ex vivo to autologous patient T cells. These TCR-modified T cells can then efficiently eliminate tumors.

For TCR-modified T-cells to mediate an efficient anti-tumor response, the source of the TCR is of decisive importance. The TCRs currently under clinical development are derived either from humans, conventional mice or are modified in vitro. This negatively impacts the affinity and specificity of the receptor leading to a poor risk/benefit profile when used in patients. In contrast, T-knife’s TCRs recognise the target similar to how they would recognise a virus in an efficient natural immune response. A phase I clinical study is planned for 2018.

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