Medigene AG announced that the Company has been issued a patent by the European Patent Office protecting its inducible Medigene T cell receptor (iM-TCR) technology, which contains a control mechanism to regulate efficacy and improve safety of its T cell receptor engineered T cell (TCR-T) therapies. TCR-T therapies have demonstrated that they can effectively kill tumor cells. However, excessive activation of T cells may lead to premature exhaustion or cell death, as well as unwanted overactivity and the potential development of inflammatory responses in the body.

The iM-TCR technology modifies the TCR to achieve control of TCR surface expression, allowing for fine-tuning of activity against tumor cells and thereby reducing potential inflammatory responses in the body. This property is of potential benefit not only to current autologous TCR-T therapy assets, but potentially also applicable to other TCR-T based modalities. Additionally, the iM-TCR technology can potentially expand the range of targets and indications of vital or more sensitive tissue origin and provide additional safety when expanding to other disease areas beyond oncology.

The T cell receptor (TCR) assembly is a complex process. In humans, TCRs consist of an alpha (a) chain and a beta (ß) chain and each chain possesses a constant and a variable part. Medigene´s proprietary iM-TCR technology prevents the normal pairing of the a and the ß chains by introduction of specific engineered sequences into the constant part of each TCR chain.

Each engineered chain is linked to an estrogen receptor sequence, which only allows the two iM-TCR chains to pair (dimerize) in the presence of Tamoxifen, and be expressed and function at the surface of TCR-T cells in a normal manner. Consequentially, to enable the iM-TCR-T cells to function in tumor cell recognition and killing, Tamoxifen administration is required but the levels required for dimerization and TCR-T function are orders of magnitude lower than the commonly used therapeutic doses. Any TCR from Medigene?s broad library of 3S TCRs can be equipped with the proprietary iM-TCR technology, which enables the function of tumor-specific TCR-T cell therapies to be finely tuned for safety and efficacy according to clinical needs.