- CAR T-cell therapy is a powerful addition to cancer immunotherapy and has offered new hope to patients with certain blood cancers.
- Scientists are looking to improve how CAR T-cell therapy is currently used, and to expand the use of CAR T cells to more blood cancers and solid tumors.
CAR T-cell therapy is a type of cellular therapy that uses a patient’s own immune system cells to rally an attack on cancer. This innovative treatment is approved for the treatment of some cancers, and researchers continue to study its potential.
The first two U.S. Food and Drug Administration-approved CAR T products, known as tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), have achieved dramatic responses in some patients with some forms of relapsed or refractory aggressive non-Hodgkin lymphoma or B-cell acute lymphoblastic leukemia (B-ALL).
Since then, additional CAR T-cell therapies have been approved. This includes brexucabtagene autoleucel (Tecartus) for mantle cell lymphoma, lisocabtagene maraleucel (Breyanzi) for large B-cell lymphoma, and idecabtagene vicleucel (Abecma) for multiple myeloma. Yescarta has also been approved for relapsed/refractory follicular lymphoma.
What are CAR T cells?
CAR T cells are made by removing some of the patient’s own immune cells and equipping them with an individualized laboratory-made receptor. When given back to the patient, these engineered cells act like a “living drug” — a one-time infusion of tailored T cells that home in on a specific protein on the patient’s cancer cells and mount an attack on the cancer.
While the treatments can have severe side effects, the availability of CAR T-cell treatments for some patients who otherwise had few options has been “totally transformative” and enables physicians to give a “message of hope,” says Caron Jacobson, MD, medical director of the Immune Effector Cell Therapy Program at Dana-Farber/Brigham and Women’s Cancer Center.
At present, the field is only in “the first leg of the CAR T journey,” as one assessment put it, with intense research underway to make the technology more widely applicable and safer.
Expanding CAR T-cell therapy to other cancers
Scientists believe there’s great promise for CAR T-cell therapy in blood cancers other than B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma, and possibly may be made effective against solid tumors as well. Several clinical studies are showing promise, Jacobson says.
In July 2020, CAR T-cell therapy (Tecartus) was approved for patients with mantle cell lymphoma following a clinical trial at Dana-Farber. Trial results showed that 87 percent of patients responded to the therapy, and 62 percent had a complete response.
In March 2021, Yescarta was approved for patients with indolent relapsed/refractory follicular lymphoma. Trial results showed that 91 percent of patients responded to the CAR T-cell therapy, including an estimated 74 percent of patients in a continued remission at 18 months.
Abecma was also approved for patients with relapsed/refractory multiple myeloma in March 2021. In trials of Abecma, the majority (72%) of patients achieved rapid, deep and durable responses.
Clinical trials of CAR T-cell therapy are ongoing, exploring this therapy in combination with other therapies, giving CAR T earlier in the treatment cycle, and minimizing side effects.
CAR T cells that take aim at multiple targets
Initially, CAR T cells were engineered to recognize just one distinctive antigen on the surface of cancer cells, such as the CD19 antigen in B-cell ALL. However, cancer cells can evolve to escape the immune attack by losing the primary target, making them invisible to the CAR T cells. Scientists are now devising CAR T cells that target multiple antigens in hopes of defeating this antigenic escape strategy.
Addressing side effects
Researchers are also working hard to understand, predict, prevent, and treat the toxic side effects that can be triggered after CAR T cells are infused into patients. Chief among them is cytokine release syndrome (CRS), a systemic inflammatory response that can be mild or severe and cause a number of complications such as fever, fatigue, low blood pressure, rapid heartbeat and pain.
‘Off-the-shelf’ CAR T cell products
A lot of research is underway to overcome a major limitation of current CAR T cell therapy: using the patient’s own immune cells to create the modified T cells.
For one thing, the patient’s immune cells may not be the most potent, due to the cancer and its prior treatments, and for another, it takes two to four weeks to process the cells before they can be given back to the patient. As a result, scientists are working toward “off-the-shelf” CAR T cell products — made from the immune cells of a healthy donor, frozen and stored. These CAR T cells could be given almost immediately when a patient needed them, says Jacobson. One healthy donor’s cells could also potentially be used to make CAR T cells for as many as 100 patients.