The first human trial went well

A gloved hand holding a pencil marks the genetic sequence on paperPost on Pinterest
In a small trial, researchers have used gene-editing technology for the first time to treat breast, colon and lung cancer in humans. Photo credit: Andrew Brookes/Getty Images.
  • For the first time, researchers have used CRISPR to replace genes in patients’ immune cells to treat cancer.
  • The participants included 16 patients with various solid cancers including breast, colon and lung.
  • The researchers isolated and cloned T-cell receptors from the patient’s blood that are able to recognize 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 replace 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 were explored in a paper published in nature10 at the Cancer Immunotherapy Society in Boston, Massachusetts.

“I consider this a big deal,” said Dr. Arelis Martir-Negron, who was 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 it can perform alteration and removal at the same time,” said Dr. Martir-Negron. “That’s the amazing thing because it’s in the past […] It was almost impossible to do both.”

said Dr. Stephanie Mandel, chief scientific officer of PACT Pharma and one of the paper’s authors Medical news today The results of the experiment showed an early proof of concept. PACT Pharma is a biopharmaceutical company developing customized therapies for the eradication of solid tumors.

“We can let the patient’s own immune system tell us how to fight cancer,” she said. “It is possible to create a completely customized treatment for each patient with cancer.”

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

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

However, T cells do not always have a receptor that matches the antigen present on the cancer cell. Different cancers have different antigens. In addition, patients also often lack enough T cells to effectively fight cancer cells.

CAR-T cell therapy is a new type of cancer treatment. Using CAR-T cell therapy, scientists engineer T cells in the lab by adding a gene for a receptor that picks up on an antigen on cancer cells and kills them. Currently, CAR-T therapy is used to treat blood cancers.

The approach detailed in the paper published in nature It is the first step in developing a treatment similar to that of solid cancers, or all non-blood related cancers.

The study, conducted with collaborators at nine academic centers, included 16 patients with various types of solid cancers, including breast, colon and lung. “These were patients that all other treatments would [had] Dr. Martyr Negron explained.

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

“Then we sequence those samples,” Dr. Mandel explained. MNTTo find mutations specific to a patient’s cancer.

Researchers have identified 175 unique cancer-specific immune receptors. They then used an algorithm to “predict and prioritize which of these mutations the immune system might actually recognize,” Dr. Mandel said. Then we move on [the] The best three of them are for treating this patient’s tumor.”

CRISPR-specific TCRs are designed to replace an existing TCR in an immune cell.

“Then we grow these cells into the billions of cells in the dish,” Dr. Mandel explained. “And then we give them back to the patient, so now we’re giving a lot of these T cells that are meant to recognize the patient’s tumor back to the patient, so they can now find and kill the cancer cells. It’s basically a living drug that you give.”

Before patients receiving CRISPR-engineered immune cells, they received conditioning chemotherapy to deplete existing immune cells.

“We had to develop platform technologies to allow us to reliably isolate these T cells and genetic material, and [TCRs], and then also to genetically reprogram that patient’s T cells with these receptors. And we also had to develop the manufacturing process to make these large numbers of these cells, right? […] We have been able to achieve this in a very short period of time of less than 5 years, and we are now hopeful that we can move forward in making this happen for all patients with solid tumours.”

Dr. Stephanie Mandel

After a month of treatment, the researchers found that the tumors of five participants had not grown. Eleven did not see any change.

In each patient biopsied after the infusion, the researchers found CRISPR-modified T cells. “They have reached their goal,” explained Dr. Martyr Negron MNT.

The majority of the side effects patients experienced, according to Dr. Mandel, were due to the adaptive therapy.

“Each patient carries their own treatment in the form of these T cells,” said Dr. Mandel. “We just have to be able to find them and then make enough of them so they have a chance of killing the cancer.”

Dr. Mandel noted that the treatment could provide lifelong protection against cancer “because the cells will continue to live in your body.”

The process from taking a patient’s blood to choosing the best TCRs took about 5 months, according to Dr. Mandel.

By automating some of the processes, Dr. Mandel believes the timeline could be shortened.

“It is a very complex process and needs further development to simplify logistics, reduce treatment cost and increase efficacy so that it can become a reality for all cancer patients,” she said.

She told us that in future research, scientists might look at what happens when patients are given a larger dose of modified T cells. They may also look for ways to make T cells tougher against tumor attacks.

“The tumor microenvironment is very, very hostile,” Dr. Mandel explained. The tumor is trying to do things to make the T cells inactive and they can do this in many different ways. But we can also use a one-step gene-editing technique to either knock out or knock out additional genes that make T cells resilient.”

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

“It’s not something that’s ready for prime time,” she said. “No treatment will change it right away.”

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