- For the first time, researchers have used CRISPR technology to replace genes in patients’ immune cells to treat cancer.
- Participants included 16 patients with different types of solid cancer, including breast, colon and lung cancer.
- The researchers isolated and cloned T cell receptors from the patient’s blood capable of recognizing tumor-specific antigens.
- After treatment, biopsies showed gene-edited T cells close to the tumors.
For the first time, researchers used CRISPR gene-editing technology to replace a gene in a patient’s immune cells to repurpose those cells to fight cancer.
Details of a small human clinical trial using this approach are explored in a paper published in
“I consider this a big deal,” said Dr. Arelis Martir-Negron, not involved in this study. The Doctor. Martir-Negron is a medical geneticist at the Miami Cancer Institute, part of Baptist Health South Florida.
“CRISPR is itself a newer technology, and the fact that they can switch and remove at the same time,” said Dr. Martyr-Negron. “This is amazing because in the past […] it would have been nearly impossible to do both.”
Dr. Stefanie Mandl, Chief Scientific Officer of PACT Pharma and one of the authors of the paper, said medical news today that the test results demonstrated an initial 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 have a completely personalized therapy for each cancer patient.”
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 don’t always have a receptor that fits the antigen on a cancer cell. Different types of cancer have different antigens. Furthermore, patients often also lack enough T cells to effectively fight cancer cells.
Chimeric antigen receptor T cell therapy (CAR-T cell therapy) is a new type of cancer treatment. With CAR-T cell therapy, scientists engineer T cells in the lab by adding a gene for a receptor that docks with the antigen on cancer cells and kills them. Currently, CAR-T therapy is used to treat blood cancers.
The detailed approach in the article published in Nature it is the first step in the development of a similar therapy for the treatment of solid cancers, or all cancers outside of blood-related cancers.
The study, conducted with collaborators at nine academic centers, involved 16 patients with different types of solid cancer, including breast, colon and lung cancer. “They were patients that all other therapies [had] failed,” explained Dr. Martyr-Negron.
The researchers took blood samples and tumor biopsies from the patients.
“And then we sequenced those samples,” explained Dr. Mandle MNT“to find specific mutations for the patient’s cancer.”
The researchers identified 175 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,” said Dr. Mandl. “Then we took [the] the top three to treat this patient’s tumor.”
The selected TCRs are CRISPR designed to replace the existing TCR in an immune cell.
“We then grew those cells to billions of cells in the dish,” explained Dr. Mandl. “And then we give them back to the patient, so now we’re giving a lot of these T cells that are all specific to recognizing the patient’s tumor back to the patient, so now they can find and kill the tumor cells. It’s basically a live drug that you give.”
Before patients received the immune cells created by CRISPR, they received a conditioning chemotherapy treatment to deplete existing immune cells.
“We had to develop platform technologies to allow us to reliably isolate these T cells and the genetic material, the [TCRs], and also genetically reprogram the patient’s T cells with these receptors. And we also had to develop the manufacturing process to make these large quantities of these cells, right? […] We have successfully done this in a very short period of time, less than 5 years, and now we look forward to being able to take this further to make this a reality for all patients with solid tumors.”
– Dr. Stefanie Mandl
One month after treatment, the researchers found that the tumors in five participants had not grown. Eleven saw no change.
In each patient biopsied after the infusion, the researchers found CRISPR-edited T cells. “They achieved their goal,” explained Dr. Martyr-Negron to MNT🇧🇷
Most of the side effects that patients have experienced, according to Dr. Mandl, it was due to the conditioning treatment.
“Each patient carries their own healing within themselves in the form of these T cells,” said Dr. Mandl. “We just have to be able to find them and do enough that they have a chance to kill cancer.”
The therapy can provide lifelong protection against cancer “because the cells will continue to live in your body,” noted Dr. Mandl.
The process of taking the patient’s blood to choose the best TCRs took about 5 months, according to Dr. Mandl.
By automating some processes, Dr. Mandl believes that the timeline can be shortened.
“It’s a very complicated process that needs further development to simplify logistics and also reduce the cost of treatment and increase effectiveness so that it becomes a reality for all cancer patients,” she said.
In future research, she told us, scientists can see what happens when they give patients a larger dose of edited T cells. They may also look for ways to make T cells more resistant to tumor attacks.
“The tumor microenvironment is very, very hostile,” explained Dr. Mandl. “The tumor tries to do things to basically make the T cells inactive, and they can do that in many different ways. But we can also use our single-step gene-editing technology to turn on or off additional genes that will make T cells resilient.”
The Doctor. Martir-Negron cautioned 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 treatments right away.”