International Business Department           Liu Bojia           October 16, 2023

  The advent of chimeric antigen receptor T-cell (CAR-T) therapy has given some patients with haematological tumours hope for a cure. By collecting a patient's own T-cells and then engineering them to carry receptors that recognise tumour antigens, scientists are able to make the T-cells more precise and efficient in their search for tumours.

  CAR-T will be more at home when dealing with blood tumours, as the blood circulation can be flooded with antigenic targets and T cells can easily come into contact with tumours. However, for solid tumours hidden in tissues, CAR-T can be a bit of a challenge. First of all, it is difficult for them to infiltrate into the tumour area, in addition, the antigens of solid tumours are often not specific enough, and the transformed T-cells may also attack healthy tissues, resulting in serious side effects. How to use CAR-T cells to treat solid tumours safely and efficiently is a new direction that scientists are trying to tackle.

  In the latest issue of the journal Science, researchers at Columbia University have innovatively proposed a way to use probiotics to guide CAR-T, a move that could help T cells find solid tumours and boost their efficiency in clearing them, which they call probiotic-guided CAR-T cell (ProCAR).

  In fact, when broken down, both bacteria and CAR-T are effective helpers in treating tumours, for example, tumour-colonising bacteria have long been used in cancer research. Thanks to the tumour-homing properties of such bacteria, they will head towards the tumour area after entering the body, and eventually colonise and grow in the tumour tissue.

  Subsequently, the bacteria attract immune cells to attack the tumour, a process that is still relatively dependent on their own T-cell levels and activity. But would the results be better if they were allowed to attract an already potent CAR-T cell? That's the question the new study attempted to address.

  The team carried out the experiment in two steps, firstly by selecting a group of bacteria that were already fond of the tumour microenvironment, a modified strain of E. coli was used in the test, these bacteria would move directionally towards the tumour and colonise the tumour microenvironment, when the population density of the bacteria reaches a certain level, the bacteria would trigger a subsequent lysis event releasing targetable antigens which include specific antigens designed in advance.

  This time, instead of carrying receptors that recognise tumour antigens, the CAR-T cells carried antigenic tags for specifically targeting tumour-colonising bacteria. The authors transplanted tumours in mice and then used this new ProCAR technology, and as a result they saw that tumours grew more slowly in the ProCAR-treated mice compared to controls, and the mice had a higher survival rate.

  They also observed similar results in colorectal cancer model mice, where ProCAR had no significant toxic side effects on the mice, did not affect their active behaviour, body weight, etc., but was able to significantly inhibit tumour growth and distal metastasis.

  In addition to the effects of the T cells themselves, the engineered bacteria additionally release chemokines that enhance immune sensitivity in the tumour microenvironment. Dr Rosa Vincent, one of the study's authors, noted that "the new study combines the strengths of the two types of therapies and compensates for their limitations by using bacteria to place targets and T cells to destroy tumours." The research team plans to conduct clinical trials in the future to validate the safety and efficacy of the ProCAR approach in humans.