Scientists at Cardiff University have used CRISPR/Cas9 genome editing technology to produce highly specific killer T cell receptors. 

Researchers at Cardiff University have replaced the regular receptors found on T cells with their own, which are geared up to better tracking down and killing cancer cells. The research reported in Blood explained how the group removed receptors that interact with immune cells and replaced them with cancer-specific T cell receptors (TCRs) using CRISPR/Cas9 technology. The research group hopes this will allow the development of better cancer immunotherapies, and support the identification of new targets.

Cancer is one of the biggest causes of mortality in the world, with 8.8 million deaths recorded in 2015. TCRs, heterodimers made up of αβ or γδ chains, have been an area of real interest as the search for new and effective cancer treatments goes on. The αβ chains of TCRs recognize foreign proteins presented by antigen presenting cells, whereas γδ chains recognize cell surface targets, including cancer antigens.

The group removed the αβ TCRs and replaced them with extra cancer-specific receptors, which improved the detection and killing of cancers. During testing in the lab, the CRISPR-T cells were observed to be far more active against cancers than those expressing both αβ and γδ chains. The group is also hoping that the increased selectivity for cancers will improve the safety of treatments using the technology.

The basic structure of a T cell receptor (TCR), which is far smaller in stature than a B cell receptor.

CRISPR has long been touted as the heir to the Nobel Prize throne, but it has missed out until now – most recently to research looking at the mechanisms underlying circadian rhythm. Maybe its use in the development of a powerful anticancer therapy will see it receive the recognition that so many in the field believe it deserves.

This research goes a step further than much of the work being carried out in the biotech sector. At the moment, Adaptimmune, which is modifying the variable regions of T cells, Autolus and its engineered T cell immunotherapies and Immunocore’s ImmTAC technology are companies leading the T cell therapies field.

This is exciting news for the cancer field, which could benefit hugely from the study’s findings – whether the technology is spun out and developed by the researchers or taken forward by others in the field.


Images – crystal light / shutterstock.com; ellepigrafica / shutterstock.com

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