When the first chimeric antigen receptor T-cell (CAR-T) therapy was approved in 2017, there was a general expectation that T-cell receptor T-cell (TCR-T) therapies would follow shortly afterwards and would greatly expand the range of addressable antigens. Despite considerable efforts, CAR-T therapies are still limited to haematological cancers expressing extracellular antigens, such as CD19 or B-cell maturation antigen (BCMA).

Autologous TCR-T therapies can be engineered to target intracellular as well as extracellular peptide antigens presented on the cell surface by human leukocyte antigens (HLAs) and can be more readily used in solid tumors as well as in haematological cancers.

Progress has been slow, however, given the complexities involved in both product design and process development. A decade ago, the field grappled with the issue of toxic and sometimes fatal cross-reactions between epitopes present in proteins expressed in healthy tissue and those contained in the targeted tumor antigens. More recently, the great challenge has been to ensure that engineered TCR-T cells are healthy enough to expand and persist once transferred back into patients.

This year marks an important milestone for the field, as the FDA is due to grant – or deny – approval of Adaptimmune’s T-cell receptor (TCR) T-cell (TCR-T) therapy Afamitresgene autoleucel (afami-cel) for treating melanoma by 4 August 4.

In this episode, we trace the development of the TCR-T technology and sketch out its future possibilities with Selwyn Ho, CEO of TCR-T therapy developer Medigene.

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