"Small scissors" are expected to fight cancer

3D image of the CRISPR gene editing system Source: University of Pennsylvania School of Medicine
Scissing HIV, editing RNA, responding to antibiotic resistance... Gene Scissors (CRISPR gene editing technology) is expanding.
recently, "gene scissors" seem to have opened a new chapter: scientists have improved cancer immunotherapy using two cutting-edge methods, CRISPR, which edits DNA, and T-cell therapy, which uses the immune system Sentinel to destroy tumors.
-edited immune cells continue to exist, thrive, and continue to function months after treatment in cancer patients. The paper was published online in Science.
is the first clinical trial in the United States to test gene editing methods in humans. Researchers at the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center presented the results of their Phase I clinical trial in which three patients were treated with gene-edited CAR-T.
, a cancer expert at the University of Pennsylvania and co-author of the paper, said the clinical trial, which has under years of regulatory scrutiny, aims not to cure cancer but to verify that the treatment is safe and feasible.
Gene-edited T-cell therapy is a revolutionary cancer treatment that provides long-term relief for blood-related cancers such as leukemia and lymphoma," Jennifer Doudna of the University of California, Berkeley, and colleagues said in a related commentary published at the same time.
so far, it is unclear whether CRISPR-edited T-cells can be tolerable to patients and thrive after re-injection into the body. Doudna said the new findings answer some questions and highlight the potential to accelerate the development of gene editing therapy.researchers developed CAR-T cell therapy in 2010, when they added T-cells from three patients with chronic leukemia to THEIR DNA and implanted them in patients. The end result was remarkable, with two patients still alive.
CAR-T cell therapy is the insertion of embedded antigen-subject genes that help inject T cells attach to the surface of cancer cells with specific proteins and destroy them. Two CAR-T cell therapies have now been approved for the treatment of leukemia and lymphoma.
over time, the limitations of this treatment begin to show. Edward Stadtmauer, a blood cancer expert at the University of Pennsylvania and co-author of the new paper, said the treatment is not helpful for every cancer patient, and that even those who have temporary effects will relapse.
, the researchers tried to use CRISPR to knock out selected genes and add DNA in the hope of making T cells stronger and longer lasting.
but CRISPR also has its own uncertainty - the "off-target" effect, in which unplanned DNA is modified. No one knows if T cells with sliced genes can survive in the human body. Although Fortai Pharmaceuticals and CRISPR Therapeutics announced that two patients who used CRISPR editing cells to treat hereditary blood disease were in good condition, few details were revealed, Science reported.
June, Stadtmauer and others targeted a protein NY-ESO-1 and began looking for patients where tumors produced the protein, which the researchers added to their T-cells as a target gene. Patients also need to carry a specific human leuperocyte antigen, an immune gene complex that helps inject T-cells proliferate.
four eligible patients screened by the researchers were all very ill, which is the standard for the new treatment. But a sarcoma patient in his 30s, who was preparing cells in the lab (the whole process takes four to six weeks), was too ill to be treated and was admitted to a hospice and died a short time later.
, three patients took part in the trial., researchers used CRISPR technology to successfully edit the immune cells of three cancer patients, according to a report in the Journal of Chinese Science. This time, the researchers used CRISPR and a joint strategy to integrate new DNA into immune cells.
data showed that the patients involved in the trial were two women and one male, both over the age of 60. One had sarcoma and two had multiple myeloma, and they received a gene-editing cell transplant last year.
to speed up the patient's T-cell fight against disease, the researchers used CRISPR to knock out two genes that encode T-cell receptors and destroy a protein called PD-1. PD-1 suppresses the immune response and eliminates its effects, while destroying the protein enhances the ability of T cells. They then inserted a gene for another T-cell receptor, NY-ESO-1.
close monitoring of patients confirms that CRISPR technology has under-targeted changes. Over time, however, the number of cells with unexpected DNA changes gradually decreases.
, CRISPR-edited cells survived for at least nine months, compared with about two months for CAR-T cells in the study. Imaging showed "healthy T-cells," June said, and in laboratory studies, they fought off cancer months after being injected.
"This is the first time that CRISPR technology has been proven to target multiple genes in humans at the same time, and its potential to treat many diseases that cannot be treated or cured." June told China Science Daily.
In an interview with China Science Daily, Gu Feng, a researcher at Wenzhou Medical University's School of Ophthalmology, also said that gene editing offers hope for the treatment of diseases that have no clinical intervention methods, and that to ensure the safety of the technology, efforts should be made to reduce the off-target effect of gene editing and improve targeting, efficiency and fidelity.but June admits that the benefits are limited for these patients, one of whom has died and the other has worsened. After receiving combination therapy, the best response was for a sarcoma patient whose primary tumor shrunk, although his cancer later developed.
" We obtained data from three patients involved in clinical trials that showed that multiple gene edits could be successfully and accurately edited, allowing the resulting cells to survive longer in the human body and demonstrating the ability to continuously attack and kill tumors. "Research has shown that this treatment strategy may be safe and feasible. The
scientists agreed that by this standard, it had succeeded. Fyodor Urnov, a gene editing expert at the University of California, Berkeley, who was not involved in the study, said the study was the first of its kind in the United States and was a decisive turning point.
you turn off the genes, those T-cells start doing amazing things," said Antoni Ribas, an oncologist at the University of California, Los Angeles. "The researchers analyzed a number of potential causes, including the small number of patients treated, the possible limitations of choosing NY-ESO-1 as a target, and the inability to knock out all three genes in many cells.
anyway, Doudna told China Science that STadtmauer et al.'s CRISPR gene-edited cell combination therapy has long-term clinically proven safety, paving the way for the next generation of cell-based therapy.
more and more gene therapistes have been shown to be safe and effective, the barriers to clinical transformation will be mainly in cell manufacturing and management. Recombining the production process of engineered cells and developing new CRISPR delivery strategies to change the targeted cells in the body are key to reducing costs and increasing access to these revolutionary treatments. Doudna said. (Source: Tang Feng, China Science Journal)
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