A clinical trial using genetically-modified white blood cells is now underway in China for lung cancer.

The trial, led by Dr. You Lu at the West China Hospital, enrols patients with advanced lung cancer, for whom chemotherapy, radiation therapy, and other treatments have failed.

What has grabbed headlines around the world is the way the trial proposes to modify the white blood cells – by using what’s called “CRISPR”. You can think of CRISPR as very precise molecular scissors. It allows researchers to edit DNA by cutting out, or adding in, different sequences.

In this clinical trial, Dr. Lu and his team are using CRISPR to cut out the gene for “PD-1” in white blood cells (more specifically, a type of white blood cell called T-cells).

PD-1 is present on the surface of T-cells to stop T-cells from attacking healthy cells in your body. While under normal circumstances this is very useful, cancer cells have taken advantage of this system to “escape” from being attacked by T-cells. So, if PD-1 is deleted from the T-cells, then the T-cells could recognize and defeat the cancer.

So what does this treatment involve? First, the researchers will take blood from the patients, and then collect the T-cells from the blood. Then, they will knockout the PD-1 gene from these cells using CRISPR. The researchers will then multiply the edited cells in the lab, and then inject the cells back into the patient’s bloodstream. These cells should home-in on the cancer cells, and subsequently kill them.

Two FDA-approved drugs, called Nivolumab (trade name: Opdivo) and Pembrolizumab (trade name: Keytruda), also target PD-1, but only by binding to it. This is not as extreme as deleting the gene for PD-1 altogether, which is what Dr. Lu is proposing in his trial using CRISPR. So hopefully, the CRISPR method would be even more effective in treating cancer than these drugs.

At this very early stage of clinical trials (“Phase 1”), the aim of the study is primarily to study the safety of the treatment, and to determine what doses can be tolerated by the patients. Only a small number of participants will be recruited (10-15 patients), and they will be followed for 6 months to see whether the treatment has any adverse side-effects.

Some possible side-effects may be an excessive autoimmune response, where the T-cells start attacking healthy organs, given the role of PD-1. However, for all intents and purposes, cancer cells are technically “foreign” cells in the body, so the edited T-cells should attack them more than they do healthy ones. Hopefully with the right dose, the researchers can maximise the attack on the cancer cells, with minimal damage on healthy organs. At this early stage, this is merely speculation – no results from this trial have been reported so far.

Here’s a link to the trial and the criteria for entry into the study, if you are interested in learning more.

This clinical trial marks the first use of CRISPR in humans. Many more developments of CRISPR in cancer therapy are on the horizon. Three clinical trials to knockout PD-1 using CRISPR to treat bladder, prostrate, and renal cancers has been proposed in China, currently pending approval. There has also been talks of a clinical trial starting in the US this year to knockout 3 different genes (one of which is also PD-1) using CRISPR, although the details of this are currently not available.

Article edited by Jack Simpson.

Feature photo designed by Freepik