18. Putting solid tumours under the T-knife: how a next-gen TCR aims to crack them

Engineered T-cell receptor (TCR) therapies promise to do for solid tumours what chimeric antigen receptor T-cell (CAR-T) therapies have done for haematological malignancies.

The two approaches are conceptually similar – each involves the isolation and modification of patients’ T-cells to recognise and kill tumour cells. The main difference lies in the types of antigens they can recognise. Whereas CAR-T therapies are currently confined to a handful of extracellular antigens expressed on the surface of malignant (and healthy) B-cells, TCR therapies can target a whole universe of intracellular antigens, fragments of which are presented on the cell surface as peptide fragments by major histocompatibility complex (MHC) molecules.

Ensuring these highly engineered cells can persist, expand and operate effectively within the immunosuppressive tumour microenvironment in patients has been a complex challenge. But the current generation of therapies is starting to show promising results.

In this episode of BioBiz Buzz, Elisa Kieback, co-founder and Chief Technology Officer at T-knife Therapeutics, joins your host Cormac Sheridan to discuss how TCR cell therapies work and what they can do, and how the founders of the Berlin-based company came up with its distinctive name.

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Chapters

• 0:04 Setting The Stage: TCR Vs CAR-T
• 2:47 The Meaning Behind T-Knife
• 4:59 Why TCRs For Solid Tumours
• 9:58 First-In-Human Trial Design
• 13:56 Safety Risks And Management
• 17:49 Why PRAME Is An Attractive Target