A new CRISPR cancer treatment has been tested in humans for the first time


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Previous studies have used gene editing technology CRISPR To remove genes from immune system cells to make them better at fighting cancer. Now, it owns PACT Pharma and UCLA used CRISPR to remove genes and add them to these cells to help them recognize the patient’s tumor cells.

Anthony Ribas, co-author of the study, “It is perhaps the most complex treatment ever undertaken in a clinic.” Tell nature. “We’re trying to build up an army of the patient’s own T cells.”

T cells are our immune systems’ defense against cancer.

Natural cancer killers: Our bodies are made up of trillions of cells. These cells grow and reproduce through cell division, and when they get old or become damaged, they die and new cells take their place.

Cancer cells contain genetic mutations that prevent them from dying in time — instead, they multiply uncontrollably, which can cause them to form clumps or spread to other parts of the body and crowd out healthy cells.

Our immune system has a built-in defense against cancer: T cells. These are a type of white blood cell that has proteins on their surfaces, called “T-cell receptors,” that attach to certain cancerous or foreign cells, prompting the T-cell to attack and kill them.

the challenge: However, T cells are not perfect.

In part because cancer cells look so much like healthy cells, they’re adept at flying under the immune system’s radar. Tumor cells can also release chemical signals that make them harder to heal T cells To determine.

“At some point the immune system lost the battle and the tumor grew.”

Stephanie Mandel

Sometimes cancer cells multiply too quickly T cells to keep up.

“if [T cells] “Seeing something that doesn’t look natural, they’re killing it,” lead author Stephanie Mandel, who works as an executive at PACT Pharma, told Nature. “But in patients we see in the clinic with cancer, at some point the immune system has lost the battle and the tumor has grown.”

By genetically engineering T cells to be better at detecting proteins commonly found on the surfaces of leukemia cells, researchers have been able to develop treatments — called “CAR-T cell therapies” — for people with these cancers.

No one has yet been able to find reliable, comparable proteins that work for solid tumors — each person’s cancer seems too unique for current CAR-T cell therapies to be effective.

CRISPR Enhancement: young First stage study Researchers at PACT Pharma and UCLA suggest we may be able to use CRISPR to boost our T cells’ ability to fight solid cancers.

They took blood and tumor samples from 16 patients with solid tumors in different parts of their bodies. Using genetic sequencing, they scanned the samples for mutations that were present in their tumor cells but not their blood cells.

“The mutations are different in each type of cancer,” Ribas said. “And although there are some common mutations, they are in the minority.”

“We’re trying to build up an army of the patient’s own T cells.”

Anthony Ribas

The researchers then scanned each participant’s T cells, looking for cells with receptors likely to recognize cancer mutations.

Using CRISPR technology, they knocked out a gene for an existing receptor and inserted a gene for a cancer-targeting receptor into T cells that lacked it. Once they had engineered what they thought would be enough T cells, the researchers reinfused them back into the patient.

Results: Subsequent biopsies found that up to 20% of the immune cells in the patients’ tumors were engineered T cells, suggesting that these cells were, in fact, very adept at directing the cancer.

Only two of the 16 participants experienced minor side effects—fever, chills, confusion—attributable to the T cells, but they resolved quickly.

“It is probably the most complex treatment ever done in a clinic.”

Anthony Ribas

After a month of treatment, five of the patients’ tumors were the same size as before, suggesting that the engineered cells might have a stabilizing effect on their condition.

The cancer continued to progress in 11 other patients, but the patient who received the highest dose of cells saw A short term improvement In their cancer – this could mean that the treatment would be more effective in future studies if given in higher doses.

“We just need to hit it harder next time,” Ribas said.

cold water: This small Phase 1 study indicates that engineered T cells are safe and likely to be effective, but there are still many limitations to overcome.

One problem is that while the engineered T cells she did They tend to focus on the tumor, they don’t always attack cancer cells.

“The fact that you can insert these T cells into a tumor is one thing. But if they get there and don’t do anything, it’s disappointing,” Bruce Levine, a professor of cancer gene therapy at the University of Pennsylvania, who was not involved in the study, said. WIRED said.

Another reason is that the treatment is expensive, complex and time-consuming — it took the researchers an average of just 5.5 months to determine which mutations to target with CRISPR after sequencing a patient’s cells.

“You can build on this. You can make it better, more efficient, faster.”

Katie Radwani

I look forward: These hurdles are not insurmountable, and now that researchers have shown that CRISPR can be used to engineer cancer-targeting T cells, future studies can take the approach to the next level.

“You can build on this,” oncologist Katie Rezvani, who was not involved in the study, told Medical Express. “You can make it better, more efficient, and faster.”

One day, engineered T cells may allow doctors to protect their patients from recurrence while treating their existing cancers.

“We’re reprogramming the patient’s immune system to target their cancer,” Mandel TIME said. “It’s a living drug, so you can give a single dose and get optimal protection for life [from the cancer]. “

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