International Business Department           Liu Bojia           August 2, 2023

  T-cells are an important line of defence against pathogens in the human body, and at the same time their role in anti-tumour is not to be underestimated, by recognising tumour antigens and then killing cancerous cells.Impaired or inefficient T-cell function is one of the prerequisites for the development of tumours, and cellular therapies similar to Chimeric Antigen Receptor T-cells (CAR-T) are designed to target tumour antigens with high precision through in vitro genetic engineering, and thus to clear tumours. antigens as a means of clearing tumours by designing high-precision killer T cells through in vitro genetic engineering.

  Despite the power of T cells, scientists have now found that they can usually only recognise and target a single tumour antigen, and if certain cancer cells do not express the specific antigen recognised by the T cell, the T cell will miss them.

  Many researchers have been envisioning a T cell that can target multiple tumour antigens, such as artificially constructed dual-target CAR-T cells. T cells that naturally target multiple tumour antigens are "hard to find", and in a recent major paper in Cell, a collaboration between scientists in the UK and Denmark found that such cells exist naturally, particularly in cancer survivors, who have T cells that target multiple tumour antigens. They can often attack multidimensionally, and as soon as a tumour exhibits one of the many targets, it is recognised and removed by the T cells.

  Of course, the discovery of these T-cells did not come by accident, but was the result of a 10-year clinical trial conducted by a team of researchers. In the trial, 31 tumour patients were treated with tumour-infiltrating lymphocyte (TIL) therapy. The therapy is carried out by harvesting lymphocytes from the patient's body, expanding them outside the body, enriching them, and then delivering them back into the body.

  During the process, the researchers collected and saved some of the patients' tumour samples. And as the treatment progressed, some of the patients achieved complete clearance of their tumours, and these people became the focus of the researchers.

  They obtained new blood samples from the cured people and tested them by mixing them with the corresponding tumour samples. The results were surprising; even though some of the patients' tumours had been gone for a year, their blood still produced a strong T-cell response to the tumour.

  These extracted killer T cells can distinguish between healthy and cancerous cells with great precision. With the help of algorithmic tools, the authors found that some T-cells can recognise multiple tumour antigen proteins, and these T-cells also behave like "superheroes" in the T-cell world.

  These super T-cells have a much greater ability to recognise and act on multiple cancer types than normal T-cells. These super T-cells are only found in people who have survived cancer, and are difficult to see in patients whose cancers are still progressing.

  This also implies that super T cells are notoriously linked to complete tumour clearance, and may even be an important driver of cancer recovery. Of course, the authors also stress that not all patients clear their tumours with TIL therapy, it just so happens that those who are cured by this therapy somehow produce these super T cells in their bodies.

  Although it's not clear exactly why, the discovery also points to a potential direction for entirely new anti-cancer therapies in the future, and the researchers believe that, similar to CAR-T therapies, scientists will be able to engineer or modify such T-cells to recognise multiple tumour antigens in the lab, especially as TIL therapies inherently require the collection of T-cells from patients, which can be iterated upon and improved upon. Until then, the research team also plans to validate this phenomenon in more patients receiving TIL therapy.