Scientists have adapted DNA-editing technology to boost the way the body fights cancer cells – in a potential breakthrough.
They modified patients’ genes to instruct cancer cells to swarm tumors using CRISPR, which is given in a single injection.
CRISPR has already been used in humans to knock out specific genes to allow the immune system to be more activated against cancer.
But the new study was able to not only remove specific genes, but insert new ones that program immune cells to fight the patient’s specific cancer.
Dr Antoni Ribas, of the University of California, Los Angeles and co-lead of the study, said: “This is a leap forward in the development of personalized cancer treatment.”
Scientists isolated genes for immune cell receptors directly from the blood of 16 patients with different tumors, then, using CRISPR gene editing to engineer these isolated genes to target mutations in cancer cells, reinserted into the patient’s own immune cells with the ability to recognize and attack the patient’s own cancer.
Scientists at pharmaceutical company PACT Pharma have used gene-editing technology to isolate and clone immune cells from cancer patients and prime them to target mutations to cancer cells.
The researchers took blood and tumor samples from 16 patients with various forms of cancer, including colon, breast and lung.
They isolated immune cells that had hundreds of mutations targeted specifically at cancers afflicting their bodies.
These have been modified to be able to target each patient’s specific tumor, which has hundreds of unique mutations.
One month after treatment, five of the participants had stable disease, meaning their tumors had not grown.
The CRISPR tool is composed of two main actors: a guide RNA and a DNA-cutting enzyme. 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 target DNA strands 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 modifies small parts of the genetic code.
Unlike other gene silencing tools, the Crispr system targets the source material of the genome and permanently silences genes at the DNA level.
The DNA break – known as a double-strand break – closely mimics the types of mutations that occur naturally, for example after chronic exposure to sunlight.
But unlike UV rays, which can cause genetic damage, the Crispr system causes a mutation at a specific location in the genome.
When the cellular machinery repairs the DNA break, it removes a small piece of DNA. 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 associates with the Cas9 enzyme and leads it to the target gene. When the guide RNA matches the DNA of the target gene, Cas9 splits the DNA, turning off the targeted gene.
Since then, the CRISPR technique has existed for about ten years and remains at the center of ambitious scientific projects.
Doctors are now exploring its application in the treatment of rare diseases and genetic disorders such as sickle cell disease.
“Generating a personalized cellular treatment for cancer would not have been possible without the newly developed ability to use the CRISPR technique to replace immune receptors in clinical-grade cell preparations in a single step,” added the Dr Ribas.
The findings give hope 1.9 million Americans who will be diagnosed with some form of cancer this year.
Approximately 290,000 women and 2,700 men will be diagnosed with breast cancer, making it the most common cancer diagnosis.
Prostate cancer is the number one cancer diagnosis in men and the second most common diagnosis overall with an estimated 269,000 cases expected this year.
Yet the technology is relatively new and raises serious ethical questions about its application to genetic remodeling.\
Medicine has entered uncharted territory in which the inherited disabilities of an embryo could possibly be removed.
Safety issues in gene editing technology research are not unknown.
There is a risk of erroneously modifying DNA or RNA in regions other than the target site, which could lead to undesirable side effects not only in the patient but also in future generations.
A major scandal rocked the world in 2019 when Chinese scientist He Jiankui was jailed after altering the DNA of twins Lulu and Nana before they were born to make them HIV resistant.
His work of manipulating the genes of human embryos has been deemed “monstrous”, “unethical” and “very dangerous”.
A group of more than 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 may still have a glimmer of hope to shut it down before it’s too late.
In 2019, a group of scientists proposed a global 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 endorsing any use of clinical germline editing unless certain conditions are met.
The conclusions of PACT Pharma were published Thursday in the journal Nature.