German biotechnology company Medigene has announced it is expanding its strategic alliance with gene and cell therapies experts bluebird bio in a deal potentially worth $1.5bn.

The partnership will focus on the development of T cell receptor-modified T cell (TCR-T) immunotherapies for the treatment of cancer. The number of projects currently underway to identify specific TCR lead candidates will increase from four to six.

Under the deal, Medigene will receive an additional one-time payment of $8m. If successfully developed and marketed through several indications and markets, Medigene could receive up to $250m in milestone payments per TCR programme in addition to tiered royalty payments on net sales.

Medigene CEO and chief scientific officer Dolores Schendel said: “We are delighted to broaden this outstanding collaboration for the joint research and discovery of TCR lead candidates designed for the treatment of multiple cancer indications.

“Medigene is contributing its unique TCR technology platform, which encompasses multiple innovative screening and assessment tools to identify and characterise specific, non-modified TCRs to selected target antigens in a highly competitive timeframe. The expansion of this alliance further validates the efficiency and quality of Medigene’s TCR platform technology.”

The two companies first signed an agreement in September 2016. Based on the terms of their original agreement, Medigene is responsible for the discovery of TCRs for each target antigen selected by bluebird bio using its TCR technology platform. An antigen is a toxin or foreign substance which induces an immune response in the body.

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Medigene’s TCR therapies modify the patient’s own T cells to have tumour-specific T-cell receptors. The receptor-modified T cells are able to detect and efficiently kill tumour cells. By activating the patient’s T cells outside the body, genetically modifying them with tumour-specific TCRs and multiplying them, a large numbers of specific T cells are made available to patients within a short period of time.

In March 2018, Medigene announced the start of a Phase I/II trial involving TCR T therapy MDG1011 in various blood cancer indications. The company does not yet have data on the efficacy of its TCR T candidates in humans.

Bluebird Bio also recently entered an agreement with Celgene to co-develop and co-promote an anti-B-cell maturation antigen CAR T-cell therapy in the US.

Bluebird Bio chief scientific officer Dr Philip Gregory said: “As we continue to build our leadership in immuno-oncology, we value Medigene’s TCR technology platform which enables us to tackle intracellular tumour antigens not addressable by CAR Ts. Our expanded collaboration will help us broaden our pipeline of TCR lead candidates for potential future clinical development.”

Bluebird is best known for its progress in Chimeric Antigen Receptor (CAR) T-cell therapy, the other type of T-cell therapy currently in development.  Although CAR T-cell therapy has effectively brought about remission in some cancer types, it only targets membrane antigens, which represent around 1% of the total proteins expressed, whereas TCRs target any peptide resulting from cellular protein degradation. Clinical trial data suggests that TCRs can also be more effective against solid tumours than CAR T therapy.

Other companies working on TCR technologies include GlaxoSmithKline and ImmunoCellular.