Oncologist Dr. Jason Westin discusses the possibilities of CAR T-cell therapy and its potential role in future cancer care.
Jason Westin, M.D., M.S., FACP, FASCO
Professor, Department of Lymphoma & Myeloma; Lead, Lymphoma & Myeloma Service Line; Director, Lymphoma Clinical Research; Section Chief, Aggressive and Indolent Lymphoma, MD Anderson Cancer Center
What is CAR T-cell therapy?
CAR T-cell therapy stands for chimeric antigen receptor T-cell therapy. A T cell is an immune cell in our blood that protects us from infections, foreign invaders, and even cancers. Cancer is our own cells turning against us. People with weakened immune systems, such as those with HIV or previous organ transplants, are more likely to develop cancer. This shows that T cells play a crucial role in fighting cancer.
CAR T-cell therapy weaponizes T cells, enhancing their ability to attack cancer. The process involves taking a patient’s own T cells, modifying them in a lab to better recognize and kill cancer cells, and then reinfusing them into the patient. This effectively turns the patient’s own immune system into a more powerful force against cancer.
How does CAR T-cell therapy treat blood cancers specifically?
It works well in blood cancers because we can identify a target on the outside of cancerous cells. This target acts as a label that directs the CAR T cells to attack. Ideally, the target should not be found on critical normal cells, as that could cause severe side effects. Fortunately, in many cases, wiping out certain immune cells, like B cells, is survivable, and the immune system can recover over time.
A researcher identifies the target, and the patient’s blood is collected. The T cells are then modified in a lab to become CAR T cells and reinfused into the patient. These modified cells act as heat-seeking missiles that find and destroy cancer cells.
I often tell my patients that this process is like taking basic infantry soldiers and sending them to special forces training. When they return, they have the skills to recognize and eliminate cancer cells that previously evaded detection.
What types of blood cancer patients are typically eligible for CAR T-cell therapy?
We hope to continue expanding eligibility. Right now, it’s mainly used for certain blood cancers, particularly cancers of B cells, which are part of the immune system. B cells can become leukemia or lymphoma, and CAR T-cell therapy is FDA-approved for these conditions.
There is ongoing research into expanding CAR T-cell therapy for other cancers, including T-cell cancers, Hodgkin’s lymphoma, and solid tumors. Multiple myeloma, another blood cancer, is also being targeted with CAR T-cell therapy. This proves the approach works, and we hope to extend it to more cancer types in the future.
What are the potential benefits and risks of this treatment compared to other options?
The benefits can be life-changing. CAR T-cell therapy has saved patients who otherwise would not have survived aggressive blood cancers. Some of my patients are so healthy now that they don’t need to come back to my clinic. In some cases, CAR T-cell therapy can offer a cure, which is remarkable when conventional treatments have failed.
We also hope to move CAR T-cell therapy into earlier lines of treatment. Currently, many patients receive traditional chemotherapy from the 1970s before trying CAR T-cell therapy. In the future, we’d like to use these modern, targeted therapies earlier in treatment.
The risks include significant side effects. The main concern is cytokine release syndrome (CRS), where the immune system overreacts, causing fever, low blood pressure, and organ dysfunction. It looks similar to a severe infection and requires specialized care. The complexity of manufacturing CAR T cells and managing side effects limits widespread use. Right now, patients need access to specialized centers for this treatment.
How do you see CAR T-cell therapy evolving in the future for blood cancer treatment?
One way CAR T-cell therapy is evolving is that we are now evaluating it for patients who have had fewer prior treatments and even for some newly diagnosed patients. Using CAR T-cell therapy earlier in treatment may lead to better outcomes.
Another important evolution is expanding access. Many physicians are still unaware of CAR T-cell therapy or do not refer patients to specialists. Financial and logistical barriers, like the need to travel to specialized centers, also limit access. We are working to ensure that more patients can receive this potentially life-saving treatment.
Can you tell me about the ALPHA3 trial?
The ALPHA3 trial is an exciting development. Most CAR T-cell therapies today use a patient’s own cells, but this trial evaluates an allogeneic, or “off-the-shelf,” CAR T-cell therapy. Instead of modifying a patient’s cells, we use cells from a healthy donor.
There are two potential benefits to this approach. First, these cells have not been exposed to chemotherapy and may be more effective. Second, they are readily available, meaning treatment can begin immediately rather than waiting weeks for the patient’s own cells to be modified.
Another unique aspect of the trial is its eligibility criteria. Instead of waiting for a patient’s cancer to relapse visibly, we use a highly sensitive blood test called PhasED-Seq. This test can detect tiny fragments of tumor DNA before a relapse is visible on a PET scan. The idea is to intervene early — if you smell smoke, call the fire department before a full fire breaks out. This trial represents a major step toward using CAR T-cell therapy proactively rather than reactively.
