Cancer Treatment with CAR T-cell
Researchers have devised a way to amplify CAR T-cell therapy to potentially make sure cells don’t die prematurely.
Although T-cell treatments with chimeric antigen receptor (CAR) have shown promising clinical results, sustained recovery remains limited.
To extend the efficiency of CAR T cells, we create a CAR booster that includes a CAR T cell antigen combined with an immune-modulating molecule.
Studies
Researchers at Harvard Medical School and Dana-Farber Cancer Institute have figured out how to boost a revolutionary treatment that harnesses immune cells in the fight against cancer.
It potentially bypasses a defect that allows the treatment to fade away before all of the diseased cells are gone.
The researchers, Mohammad Rashidian, assistant professor of cancer immunology at Dana-Farber and radiology at HMS, postdoctoral student Taha Rakhshandehroo, and their team created a boosting protein that selectively energizes an anti-cancer cell therapy called CAR T cells.
This protein not only increases the anti-cancer activity of the cells, but also promotes the development of CAR memory T cells. It provides long-term protection against cancer, similar to the immune response after chickenpox infection or vaccination.
Cell therapy
Cancer continues to be a major global health challenge. It is one of the leading causes of death worldwide, accounting for 10 million deaths annually.
Early diagnosis, improved diagnostic tools, and better treatments have helped increase the survival rate of many types of cancer.
Immunotherapy, targeted therapies, and personalized medicine have emerged as promising approaches to cancer treatment. They provide more accurate and effective options for patients. Chimeric Antigen Receptor T Cell Therapy (CAR-T Cell Therapy) is an innovative form of immunotherapy that uses the power of the immune system to treat leukemia.
CAR-T cell therapy has shown significant success in the treatment of acute lymphoblastic leukemia (ALL), diffuse B-cell lymphoma (DLBCL), and chronic lymphocytic leukemia (CLL).
Cancer Treatment with CAR-T Cell Therapy
The cancer treatment, CAR-T cell therapy, was approved by federal regulators in 2017. This treatment works by extracting immune T cells from patients and reprogramming them with a “chimeric antigen receptor” (CAR) on the cell surface. This receptor acts as a lock and key for the protein marker on the surface of the cancer cells. This allows CAR T cells to identify and attack cancer cells after they are reinjected into the body.
But once the CAR T cells have cleared most of the cancer, their numbers fade over time, allowing the remaining diseased cells to multiply. For example, in multiple myeloma, white blood cell carcinoma, treatment with CAR T cells increases survival in the short term, but half of patients relapse within one to two years.
Within three years, most patients will see their cancer recur. The breakthrough, which has not yet been tested in humans, was made by using multiple myeloma models in preclinical studies of mice in work sponsored by the Dana-Farber’s Innovation Research Award, the Parker Institute for Cancer Immunotherapy, and the Blavatnik Therapeutic Challenge Award.
Results of studies
The results of the study are published in the journal Nature Biotechnology.
This method should be useful against other cancers, and studies are ongoing. It tests against leukemia and lymphoma. CAR T cell therapy is one of a series of relatively new cancer therapies that have revolutionized care.
Unlike traditional surgery, chemotherapy, and radiation therapy, this treatment makes the immune system a powerful weapon to fight disease. The booster protein selectively targets CAR T cells, increasing their activity and shelf life.
The couple began their work two years ago with the goal of developing a method that could quickly become clinical care. Other researchers have been tackling the problem of CAR T cell longevity for a decade by focusing on re-engineering them to extend their lifespan in the body, a strategy that has largely fallen short.
Rashidian and Rakhshandeh focused on stimulating CAR-T cells instead of changing the CAR-T cells after injection and at the desired time.
Method of study
They designed a protein that targets and stimulates CAR-T cells.
The CAR receptor is the engineered part of the CAR T cell that allows it to recognize cancer cells by identifying a specific marker on them.
The boosting protein combines the cancer marker with a molecule called IL-2, which increases the activity and longevity of T cells.
IL-2 is designed to be weak, does not affect normal T cells, and prevents toxicity.
Because the boosting protein targets CAR T cells, weak IL-2 increases their activity through proximity.
Subsequent Tests
“Sometimes in science, you see marginal differences here and there, then you do the statistics and you see the importance. For us, it was like night and day.
“Sometimes in science, you see marginal differences here and there, then you do the statistics and you see the importance. For us, it was like night and day.
How Protein Booster Works
“To prevent over-stimulation of CAR T cells, the booster protein has been adjusted to have a short circulatory half-life, just two hours before it is cleared from the body,” Rashidian said.
This gives it time to stimulate CAR T cells without overstimulating them.
This also allows for more precise dose control as soon as human trials begin – Rashidian has begun seeking funding for Phase 1 trials to measure efficacy and safety.
With such a short circulator-boosting lifespan, researchers can easily adjust doses based on how patients responded in the trial, Rashidian said.
Saving the lives of patients
“It works beyond what we expected,” Rashidian said. It’s incredibly strong. I am very hopeful that this will save the lives of the patients.”