Nature: Gene editing + CAR-T join forces! Targeted elimination of cancer cells, the most sophisticated gene therapy in history: personalized treatment for cancer

CAR-T cell therapy has always been widely known, CAR-T cells have many advantages in tumor immunotherapy, it can use non-restrictive forms to specifically recognize and kill cancer cells expressing specific antigens, single chain antibody fragment (scFv) as the antigen recognition segment of CAR can recognize different types of antigens, including non-protein antigens such as sugars and lipids, lipid antigens on the surface of tumors can also be used as targets.
It is no longer limited to protein antigens
.

However, the current application of CAR-T cell therapy has certain limitations
due to the lack of surface proteins as targets in solid tumors.
According to Nature News, recently, the research team of the American biopharmaceutical company PACT Pharma and other institutions used CRISPR/Cas9 gene editing technology to genetically engineer T cells, so that T cells can recognize mutant proteins unique to a single patient's tumor, and achieve specific treatment
for solid tumors.

The study, published in Nature, is titled "Non-viral precision T cell receptor replacement for personalized cell therapy" (Figure 1).

Studies have confirmed that CRISPR gene editing can be used to alter immune cells so that they can recognize mutated proteins
specific to human tumors.
These cells can then be safely released in the body to destroy their targets
.

Figure 1 Research results (Source: [1])

The study is the first attempt to combine two hot areas of cancer research: the creation of personalized treatments through gene editing, enabling T cells to recognize mutant proteins unique to individual patients' tumors, enabling specific treatments
for solid tumors.
The method was tested
in 16 patients with solid tumors.
The researchers developed personalized treatments
for each patient for specific weaknesses in the subjects' tumors.

The study focused on the immune system's T cells, which "patrol" within the body and check other cells for problems
.
T cells use proteins called receptors to effectively sniff out abnormal cells
that show signs of infection or have become cancerous.
T cells are difficult to find cancer, viruses are markedly different from the human body, and the manifestations of cancer are more subtle and less perceptible because cancer cells are damaged versions
of our own cells.
The idea of the therapy is to increase the level at
which T cells find cancer cells.
Because each patient's tumor has its own specificities, it must be tailored
to each patient.

First, the researchers looked for rare T cells in the patient's blood that already had receptors that could sniff out cancer; The researchers then collected other T cells that could not find cancer and redesigned their original receptors, and found other problems or infections, replaced by receptors of T cells that can localize cancer cells; Finally, these modified T cells are placed back into the patient to look for tumors
.

Converting T cells into a form that can capture cancer requires sophisticated gene-editing operations to remove the genetic instructions that build the old receptor and provide them with instructions for the new receptor
.
The advanced gene-editing technology CRISPR enables targeted elimination of CAR-T cancer cells, which acts like a pair of molecular scissors — allowing scientists to easily manipulate DNA
.

"This is probably the most complex treatment ever tried clinically," said study co-author Antoni Ribas, a cancer researcher and physician at UCLA.

”

The trial, which involved patients with colon, breast or lung cancer who did not respond to other treatments, was designed to test the safety and feasibility of the technique and show that modified cells are looking for a pathway
into the tumor.
In the end, the condition of 11 patients continued to deteriorate, but the condition of the other 5 patients was stable
.
However, larger studies are needed to determine the correct dosage and its true effects
.

"This is a milestone in developing personalized treatments for cancer," said Dr.
Anthony Ribas, one of the researchers at the University of California, Los Angeles, who tested the method
developed by Pact Pharma.
Dr Manel Juan, head of immunology services at Barcelona Clinic Hospital, said it was a "significant piece of work" and undoubtedly one of the most advanced in the field, opening the door
to the use of personalized treatment options for many types of cancer and potentially many other diseases.
”

The researchers who developed CRISPR won the 2020 Nobel Prize in Chemistry (Figure 2).

CRISPR is known as genetic scissors and is also known as a tool to
rewrite the code of life.
Researchers alter the DNA
of animals, plants and microbes with extreme precision.
This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies, and could make dreams of curing genetic diseases a reality
.
If researchers want to understand the inner workings of life, they need to modify genes in cells
.
This used to be a time-consuming, difficult, and sometimes impossible task
.
Using the CRISPR/Cas9 scissors, it is now possible to change the life code
in a matter of weeks.

Figure 2 2020 Nobel Prize in Chemistry (Source: [3])

"This genetic tool has tremendous power, and it affects us all
.
Not only has it revolutionized basic science, it has also spawned innovative crops that will lead to breakthrough new medical therapies," said
Claas Gustafson, chairman of the Nobel Committee on Chemistry.

As scientific research shows, the discovery of these genetic scissors was unexpected
.
While Emmanuelle Charpentier was studying Streptococcus pyogenes, she discovered a previously unknown molecule, tracrRNA
.
Her work shows that tracrRNA, part of the bacteria's ancient immune system, CRISPR/Cas, disarmed
the virus by cutting its DNA.

Since Charpentier and Doudna discovered the CRISPR/Cas9 scissors in 2012, their use has
exploded.
The tool has led to many important discoveries in basic research, and plant researchers have been able to breed crops
that are resistant to mold, pests and drought.
In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure hereditary diseases is about to come true
.
These genetic scissors usher in a new era in life sciences and bring the greatest benefits
to humanity in many ways.