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First Clinical Trial Of Genetically Modified Cancer-Fighting Immune Cells Shows Great Promise


Dr. Alfredo Carpineti

Senior Staff Writer & Space Correspondent

clockFeb 7 2020, 17:32 UTC

Artist's impression of T-cells attacking a cancer cell.

American researchers have concluded the first phase I trial of a novel approach in the fight against cancer. T-cells, a type of immune cell, were genetically modified using the CRISPR-Cas9 technique to attack cancer cells. The team tested the method on three patients in their 60s with advanced cancer, whose t-cells were still actively fighting the cancer up to nine months after the first injection.

Cancer is an umbrella term for a large group of diseases where our own cells multiply uncontrollably. Given that they are made of the same stuff as our own bodies, the immune system doesn’t recognize cancer cells as dangerous and thus doesn’t attack them.


Efforts in the last decade have focused on finding ways to teach the immune system how to recognize and attack cancer cells. In this work, as reported in Science, the team achieved this by removing three genes from T-cells that would otherwise prevent them from attacking the cancer. The team then used a virus to arm these T-cells to attack a protein typically found on cancer cells.

“Our data from the first three patients enrolled in this clinical trial demonstrate two important things that, to our knowledge, no one has ever shown before. First, we can successfully perform multiple edits with precision during manufacturing, with the resulting cells surviving longer in the human body than any previously published data have shown. Second, thus far, these cells have shown a sustained ability to attack and kill tumors,” senior author Professor Carl June, MD, the director of the Center for Cellular Immunotherapies in the Abramson Cancer Center and director of the Parker Institute for Cancer Immunotherapy at the Perelman School of Medicine at the University of Pennsylvania, said in a statement.

The work is good news but it is too early to know just how important this new tool will be as a cancer therapy. It is important to remember that a phase I trial is designed to test the safety of a treatment. More work is necessary to establish its efficacy and making sure it is truly safe. When the trial ended, two patients were still receiving other treatments and the third one had died. The team also discovered two off-target edits in the patient genome. While this occurred in fewer than 1.5 percent of cells, the unintended changes will need to be explored further. 

“By using new technologies that can change genes, it looks like we can now engineer immune cells outside the body to safely contribute to cancer treatment,” Professor Justin Stebbing, from Imperial College London, who was not involved in the study said in a statement.


“However, as with all these sorts of early reports it requires confirmation in much larger studies. The most important finding of the study is that these new engineered T cells don’t seem to trigger an immune response against them, which in turn could have led to lots of side effects. Whether it works in a broader population remains to be seen.”

The team worked closely the National Institutes of Health, the FDA, and Penn’s institutional review board and institutional biosafety committee to make sure that patient safeguards were in place and every step followed the approved regulations.

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