At Technical University of Munich (TUM) Successful Genetical modification of a patient’s own immune cells, T cell receptors, using CRISPR-Cas9 gene editing tool. The engineered T cells are very similar to the physiological immune cells.

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At Technical University of Munich (TUM) Successful Genetical modification of a patient’s own immune cells, T cell receptors, using CRISPR-Cas9 gene editing tool. The engineered T cells are very similar to the physiological immune cells.

July 17, 2019 by 2012pharmaceutical

At Technical University of Munich (TUM) Successful Genetical modification of a patient’s own immune cells, T cell receptors, using CRISPR-Cas9 gene editing tool. The engineered T cells are very similar to the physiological immune cells.

Reporter: Aviva Lev-Ari, PhD, RN

Targeted exchange using the CRISPR-Cas9 gene scissors

The problem with conventional methods is that the genetic information for the new receptors is randomly inserted into the genome. This means that T cells are produced with both new and old receptors or with receptors having one old and one new chain. As a result, the cells do not function as effectively as physiological T cells and are also controlled differently. Moreover, there is a danger that the mixed chains could trigger dangerous side effects (Graft-versus-Host Disease, GvHD).

“Using the CRISPR method, we’ve been able to completely replace the natural receptors with new ones, because we’re able to insert them into the very same location in the genome. In addition, we’ve replaced the information for both chains so that there are no longer any mixed receptors,” explains Kilian Schober, who is a lead author of the new study along with his colleague Thomas Müller.

Near-natural properties

Thomas Müller explains the advantages of the modified T cells: “They’re much more similar to physiological T cells, yet they can be changed flexibly. They’re controlled like physiological cells and have the same structure, but are capable of being genetically modified.“ The scientists have demonstrated in a cell culture model that T cells modified in this way behave nearly exactly like their natural counterparts.

“Another advantage is that the new method allows multiple T cells to be modified simultaneously so that they’re able to recognize different targets and can be used in combination. This is especially interesting for cancer therapy, because tumors are highly heterogeneous,” Dirk Busch adds. In the future, the team plans to investigate the new cells and their properties in preclinical mouse models, an important step in preparing for clinical trials with humans.

Original Publication

Kilian Schober, Thomas R. Müller, Füsun Gökmen, Simon Grassmann, Manuel Effenberger, Mateusz Poltorak, Christian Stemberger, Kathrin Schumann, Theodore L. Roth, Alexander Marson and Dirk H. Busch: Orthotopic replacement of T-cell receptor ɑ- and β-chains with preservation of near-physiological, Nature Biomedical Engineering, June 12, 2019, DOI: 10.1038/s41551-019-0409-0

SOURCE

https://www.tum.de/nc/en/about-tum/news/press-releases/details/35560/