Scientists have tailored DNA-editing technology to turbocharge how the body fights cancer cells — in a potential breakthrough.
They modified patients’ genes to instruct cancer-fighting cells to swarm tumors using CRISPR, which is given as a one-off injection.
CRISPR has been previously used in humans to remove specific genes to allow the immune system to be more activated against cancer.
But the new study was able to not only take out specific genes, but insert new ones which program immune cells to fight the patient’s own specific cancer.
Dr Antoni Ribas, from the University of California, Los Angeles and co-leader of the study said: ‘This is a leap forward in developing a personalized treatment for cancer.’
Scientists isolated immune cell receptor genes directly from the blood of 16 patients with different tumors and then, using CRISPR gene editing to engineer those isolated genes to target cancer cell mutations, infused them back into the patients’ own immune cells with the capacity to recognize and attack the patient’s own cancer.
Scientists at pharmaceutical company PACT Pharma used gene-editing technology to isolate and clone cancer patients’ immune cells and prime them to target mutations on cancer cells.
Researchers took blood and tumor samples from 16 patients with various forms of cancer including including colon, breast and lung.
They isolated the immune cells that had hundreds of mutations targeted specifically at the cancers plaguing their bodies.
These were modified to be able to target each patient’s specific tumor, which have hundreds of unique mutations.
One month after treatment, five of the participants experienced stable disease, meaning their tumors had not grown.
The CRISPR tool consists of two main actors: a guide RNA and a DNA-cutting enzyme. The guide RNA is a specific RNA sequence that recognizes the target piece of DNA to be edited and directs the enzyme, Cas9, to initiate the editing process.
Cas9 precisely cuts the target strands of DNA and removes a small piece, causing a gap in the DNA where a new piece of DNA can be added.
HOW DOES CRISPR WORK?
Crispr technology precisely changes small parts of genetic code.
Unlike other gene-silencing tools, the Crispr system targets the genome’s source material and permanently turns off genes at the DNA level.
The DNA cut – known as a double strand break – closely mimics the kinds of mutations that occur naturally, for instance after chronic sun exposure.
But unlike UV rays that can result in genetic alterations, the Crispr system causes a mutation at a precise location in the genome.
When cellular machinery repairs the DNA break, it removes a small snip of DNA. In this way, researchers can precisely turn off specific genes in the genome.
Scientists design the guide RNA to mirror the DNA of the gene to be edited, known as the target.
The guide RNA partners with the Cas9 enzyme and leads it to the target gene. When the guide RNA matches up with the target gene’s DNA, Cas9 splices off the DNA, shutting the targeted gene off.
Since the CRISPR technique has been around for about a decade and remains at the center of ambitious scientific projects.
Doctors are now exploring its application in treating rare diseases and genetic disorders such as sickle cell disease.
‘The generation of a personalized cell treatment for cancer would not have been feasible without the newly developed ability to use the CRISPR technique to replace the immune receptors in clinical-grade cell preparations in a single step,’ Dr Ribas added.
The findings give hope for 1.9 million Americans who will be diagnosed with some form of cancer this year.
Roughly 290,000 women and 2,700 men will be diagnosed with breast cancer, which makes it the most common cancer diagnosis.
Prostate cancer is the leading cancer diagnosis among men and the second most common diagnosis overall with about 269,000 expected cases this year.
Still, the technology is relatively new and poses some hefty ethical questions about its application for genetic remodeling.
Medicine has entered uncharted territory in which hereditary disabilities in an embryo could possibly be edited out.
Safety issues in gene editing technology research are not unheard of.
There is a risk of erroneously changing the DNA or RNA in regions other than the target site, which could result in unwanted side effects not just in the patient but in future generations.
A major scandal rocked the world in 2019 when Chinese scientist He Jiankui was imprisoned after modifying the DNA of twin girls Lulu and Nana before birth to make them resistant to HIV.
He’s work to manipulate the genes of human embryos was deemed ‘monstrous,’ ‘unethical,’ and ‘very dangerous’.
A group of over 100 scientists in China blasted He’s work in 2018: ‘Conducting direct human experiments can only be described as crazy.’
The group added, ‘Pandora’s box has been opened. We still might have a glimmer of hope to close it before it’s too late.’
In 2019, a group of scientists proposed a worldwide moratorium on human germline editing.
They wrote: ‘By ‘global moratorium’, we do not mean a permanent ban. Rather, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.’
PACT Pharma’s findings were published Thursday in the journal Nature.