Longevity Briefs: Generating CAR-T Cells in Less Than 24 Hours

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: In 2017, a new era of cancer treatment dawned when the first CAR-T cell therapy was given approval by the American Food and Drug Administration (FDA). However despite early excitement, the results of initial trials were underwhelming, with the treated cancer patients regularly relapsing.

CAR-T cell therapy is a type of cancer treatment in which a patient’s own immune cells are genetically modified to more effectively fight cancerous cells. The immune cells involved are known as T cells, and they play an integral part of the adaptive immune system, helping to recognise and organise a defence to destroy foreign pathogens. In CAR-T cell therapy, the T cells are genetically modified to express something called a chimeric antigen receptor (CAR) on their surface; a molecular tool, which gives the T cell a greater ability to recognise specific markers, or antigens, on the surface of cancer cells.

The greater the chance of detecting cancerous cells, the greater the chance of eradicating the cancer.

In order to arm the cells with this cancer-busting tool, the T cells are removed from the body and isolated. This is followed by a complex 9 day procedure, where the T cell population is ‘activated’, a process in which a foreign antigen is presented to the T cell, triggering expansion. This expansion is necessary as it allows the molecular transport systems, known as viral vectors, to infect the T cells, and deliver the CAR encoding gene into their system.

Unfortunately, due to cellular processes triggered by the T cell activation, as well as the sheer length of time this procedure takes (9 days is a long time in the world of cell culture!), the ability of these CAR-T cells to effectively fight the cancer diminishes. This is thought to be one of the key reasons for the underwhelming initial results of CAR-T cell trials.

What did the researchers do: In a study recently published in Nature, a team of researchers based in Philadelphia, US, hypothesised that by simplifying the procedure, they would be able to produce more potent CAR-T cells to tackle the cancer once re-infused back into the patient’s body. This simplification involved the elimination of the activation stage and reduction in the overall time it took to complete the entire process by recruiting a different type of viral vector to deliver the CAR gene to the T cells.

Unlike other viral vectors, lentiviral vectors are able to infect quiescent T cells, or T cells which are not rapidly proliferating. By using lentiviral vectors, the researchers were able to deliver the CAR gene to the T cells without having to undertake the long and laborious steps of activating and expanding the T cell population.

Key takeaway(s) from this research: Not only did this new methodology produce highly functioning CAR-T cells, the technical advancement that these results demonstrate has huge implications for the practical application of CAR-T cell therapy as an effective weapon in the cancer treatment arsenal.

The most notable takeaway is the fact that what once took 9 days to carry out, can now be done in less than 24 hours. Logistically, this means that CAR T cell manufacturing will no longer be constricted to specialist laboratories, but can be carried out in local hospital labs, making the treatment far more accessible.

These results demonstrate the potential for a vast reduction in the time, materials and labour required to generate CAR T cells, which could be especially beneficial in patients with rapidly progressive disease and in resource-poor healthcare environments
Source: Rapid manufacturing of non-activated potent CAR T cells