CRISPR vs breast, colon and lung cancer: first-in-human trial going well

CRISPR vs breast, colon and lung cancer: first-in-human trial going well

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In a small trial, researchers have used gene-editing technology for the first time to treat breast, colon and lung cancer in humans. Image credit: Andrew Brookes/Getty Images.
  • For the first time, researchers have used CRISPR technology to substitute genes in patients’ immune cells to treat cancer.
  • Participants included 16 patients with different solid cancers, including breast, colon and lung cancers.
  • The researchers isolated and cloned T cell receptors from the patient’s blood capable of recognizing tumor-specific antigens.
  • After treatment, biopsies showed genetically modified T cells near the tumors.

For the first time, researchers have used CRISPR gene-editing technology to substitute a gene in a patient’s immune cells to redirect those cells to fight cancer.

Details of a small human clinical trial using this approach are explored in an article published in Natureand they were presented Nov. 10 at the Society for Immunotherapy of Cancer in Boston, MA.

“I see this as a big deal,” said Dr. Arelis Martir-Negron, not involved in this study. Dr. Martir-Negron is a medical geneticist at the Miami Cancer Institute, part of Baptist Health South Florida.

“CRISPR itself is a newer technology, and the fact that they can effect the switch and suppress it at the same time,” Dr. Martir-Negron said. “That’s what’s amazing because in the past […] it would have been almost impossible to do both things.

Dr. Stefanie Mandl, Scientific Director of PACT Pharma and one of the authors of the article, said Medical News Today that the results of the trial demonstrated early proof of concept. PACT Pharma is a biopharmaceutical company working to develop personalized treatments to eradicate solid tumors.

“We can let the patient’s own immune system tell us how to fight the cancer,” she said. “It is possible to offer a fully tailored therapy to each cancer patient.”

T cells are a type of white blood cells that are part of the immune system. On the surface of T cells are proteins called T cell receptors (TCRs).

TCRs can recognize antigens, such as bacteria or viruses. Receptors and antigens fit together like a lock and key. This mechanism allows T cells to destroy the bacteria or cancer cell.

Yet T cells don’t always have a receptor that matches the antigen on a cancer cell. Different cancers have different antigens. Additionally, patients often lack enough T cells to fight cancer cells effectively.

Chimeric antigen receptor T cell therapy (CAR-T cell therapy) is a new type of cancer treatment. With CAR-T cell therapy, scientists create T cells in the lab by adding a gene for a receptor that fits the antigen on cancer cells and kills them. Currently, CAR-T therapy is used to treat blood cancers.

The approach detailed in the article published in Nature is the first step in developing a similar therapy for the treatment of solid cancers, or all cancers outside of blood-related cancers.

The study, which was conducted with collaborators from nine academic centers, involved 16 patients with different solid cancers, including breast, colon and lung cancer. “They were patients that all other therapies [had] failed,” explained Dr. Martir-Négron.

The researchers took blood samples and tumor biopsies from the patients.

“And then we sequence those samples,” Dr. Mandl explained to DTM“to find mutations specific to the patient’s cancer.”

The researchers identified 175 unique and cancer-specific immune receptors. They then used an algorithm “to predict and prioritize which of these mutations can actually be recognized by the immune system,” Dr. Mandl said. “Then we resume [the] three best to treat this patient’s tumor.

Selected TCRs are engineered by CRISPR to replace the existing TCR in an immune cell.

“Then we grow these cells up to billions of cells in the dish,” Dr. Mandl explained. “And then we give them back to the patient, so now we give back a lot of these T cells which are all specific to recognize the patient’s tumor in the patient, so they can now find and kill the tumor cells. It’s basically a live drug that you give.

Before the patients were given the CRISPR-engineered immune cells, they were given a conditioning chemotherapy treatment to deplete the existing immune cells.

“We had to develop technology platforms to enable us to reliably isolate these T cells and the genetic material, the [TCRs], then also to genetically reprogram the T lymphocytes of this patient with these receptors. And we also had to develop the manufacturing process to make these large numbers of these cells, right? […] We managed to do this in a very short time, less than 5 years, and we now hope to be able to move things forward to make it a reality for all patients with solid tumors.

– Dr Stefanie Mandl

A month after the treatment, the researchers found that the tumors of five participants had not grown. Eleven saw no change.

In each patient biopsied after the infusion, the researchers found CRISPR-modified T cells. “They hit their target,” Dr. Martir-Negron explained to DTM.

The majority of side effects experienced by patients, according to Dr. Mandl, were due to the conditioning treatment.

“Each patient carries their own healing within them in the form of these T-cells,” Dr. Mandl said. “We just need to be able to find them and make enough of them that they have a chance of killing cancer.”

The therapy could provide lifelong protection against cancer “because the cells will continue to live in your body,” Dr. Mandl noted.

The process from drawing the patient’s blood to selecting the best TCRs took about 5 months, according to Dr. Mandl.

By automating certain processes, Dr. Mandl believes the timeline can be shortened.

“It’s a very complicated process that needs to be developed further to simplify the logistics, reduce the cost of treatment and increase efficiency so that it can become a reality for all cancer patients,” she said. declared.

In future research, she told us, scientists could examine what happens when patients are given a larger dose of modified T cells. They may also look for ways to make T cells more resistant to tumor attack.

“The tumor microenvironment is very, very hostile,” Dr. Mandl explained. “The tumor is trying to do things to make the T cells inactive and they can do it in different ways. But we can also use our one-step gene-editing technology to inject or knock out additional genes that will make T cells resistant.

Dr. Martir-Negron warned patients with solid cancers not to get too excited about this therapy.

“It’s not something that’s ready for prime time,” she said. “It won’t change any treatment right away.”

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