CRISPR trial in humans – a look at checkpoint inhibitors

Scientists in China led by oncologist Lu You at Sichuan University in Chengdu have started treating patients in the first ever CRISPR human trial. They have beaten out the US team from U Penn who had previously obtained approval from a bioethics committee in June but were still waiting on FDA approval.

Carried out at the West China Hospital in Chengdu, Lu You is isolating T cells from 10 patients with metastatic non-small cell lung cancer that have failed to respond to chemotherapy, radiation therapy and other treatments. To these T cells, he is introducing CRISPR-mediated genetic modifications to knock-out the Programmed Cell Death Protein 1 (PDCD1) gene, expanding them in culture, and introducing them back into the patients at escalating doses. The key aim of the trial is establishing safety and researchers will be monitoring adverse events, progression free survival, circulating tumour DNA  and other immune system activity readouts such as interferon gamma levels.

T cell therapy against cancer has amassed huge research funding and support, read the CAR T phenomenon in an old blogpost here. And checkpoint inhibition is the latest and most popular strategy to help T cells identify and kill cancer cells. See how it works in this nifty video by the Dana Farber Institute:

Although there has been a lot of success with checkpoint inhibitor drugs (see here for a list), there has also been a recent report in the New England Journal of Medicine that a combination of two check-point inhibitors (Yervoy and Opdivo, against CTLA4 and PD1 respectively) produced severe heart inflammation and damage (myocarditis) that was driven by T cells, causing death in two patients.

The patients in the China trial will not be given any checkpoint inhibitor drugs, but its still uncertain what these modified T cells are capable of once inside the body. Previous trials have however been performed with reported “unprecedented” success rates ranging around 90%. And it was very successful for this little girl named Layla. I have yet to come across the published results but am keeping my fingers crossed!


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