What is CAR T-Cell Therapy?

New Therapy Produces Remarkable Responses in Early Trials

Artwork of T cells attacking a cancer cell.

Formally known as adoptive cell transfer (ACT), this is a new therapy which involves engineering the patients’ own immune cells to recognize and attack their tumor cells. Although this type of therapy is currently experimental and has been restricted to a few small clinical trials so far, it has shown some remarkable responses in patients with advanced cancer.

How It Works

T cells, a type of immune cell, are present with receptors on their surface, called T-cell receptors, or TCRs.

Typically these TCRs bind to antigens to mount an immune response. In an attempt to use T cells for cancer therapy, T cells are collected from a patient’s own blood. Then, in the laboratory, the T-cells are modified to produce special receptors on their surface called chimeric antigen receptors, or CARs, which are able to bind to certain surface proteins of particular cancer cells. The engineered CAR T cells are harvested in the lab and allowed to increase their numbers until there are billions of them. Subsequent to the modification and harvesting, these T cells, which present with CARs that can recognize and kill specific cancer cells, are reintroduced into the patient.

These CARs are proteins that let the T cells recognize a specific protein, or antigen, on tumor cells. The engineered CAR T cells are grown up in the lab and allowed to increase their numbers until there are billions of them.

So far, how well they work seems to depend at least in part on their ability to grow and remain active in the patient after they get infused back in.

The idea of using live cells to treat cancer is actually not new. Lessons learned from results of similar therapies in the past led to gains in knowledge of how T cells work, which fueled more discoveries.

Investigators working in this field caution that there is still much to learn about CAR T-cell therapy. But the early results from trials like these have generated quite a bit of optimism.

Successes So Far

Some have likened this kind of therapy to the merging of two separate kinds of treatment: targeted antibodies, like rituximab, with their characteristic specificity; and cancer-cell-killing agents with the power of cytotoxicity--all of this with the added long-term presence of living cytotoxic T cells, to hopefully remain in circulation, monitoring for recurrence.

The research is still very new, so experts urge caution, but clinical trials have already begun using CAR T-cell therapies in the following cancers:

  • Advanced melanoma
  • Advanced acute lymphoblastic leukemia (ALL)
  • Diffuse large B-cell lymphoma

The FDA has designated CAR T-cell therapy a breakthrough therapy for ALL. It’s also being tested in relapsed and refractory non-Hodgkin lymphoma, myeloma, and chronic lymphocytic leukemia (CLL), as well as for patients with non-Hodgkin lymphoma and myeloma.

Investigators hope CAR T-cell therapy will one day become a standard therapy for certain B-cell malignancies such as ALL and chronic lymphocytic leukemia.

Researchers working with CAR-T cells have also identified this kind of therapy as a “bridge” to bone marrow transplant for ALL patients who stop responding to chemotherapy.

One trial examined the use of CAR T cells in 15 adult patients, and most of them had advanced diffuse large B-cell lymphoma. Though it was undoubtedly a small trial, optimism comes from the fact that most of these patients treated with CAR T-cells had either complete or partial responses.

There is also the hope that CAR T-cell therapy might be used to prevent relapses. Other findings that serve to fuel optimism include expansion of the treatment cells after infusion, as much as 1,000-fold in some individuals; and the presence of CAR T cells in the central nervous system, a “sanctuary site” where lone cancer cells that have escaped chemotherapy or radiation may hide.

In two patients in an NCI-led pediatric trial, for instance, the CAR T-cell treatment eradicated cancer that had spread to the central nervous system.

Side Effects

When a large number of engineered T cells are reintroduced in a patient, these T cells release cytokines in large amounts. This may cause the cytokine-release syndrome, which is characterized by dangerously high fevers and drop in the blood pressure. Cytokines are chemical signals, and cytokine-release syndrome is a common problem in patients treated with CAR T cells. Patients with the most extensive involvement of cancer prior to receiving the CAR T-cells appear more likely to have the severe cases of cytokine-release syndrome. Researchers caution that despite successes, more research is needed before CAR T-cell therapy can becomes a routine option, for patients with ALL for instance. Studies with more patients and longer follow up periods have been called for and pursued.

On the Horizon

Based on the success thus far, several research groups across the country are turning their attention to developing engineered T cells for other cancers, including solid tumors like pancreatic and brain cancers.


CAR T-Cell Therapy: Engineering Patients’ Immune Cells to Treat Their Cancers. http://www.cancer.gov/cancertopics/research-updates/2013/CAR-T-Cells.

Barrett DM, Singh N, Porter DL, Grupp SA, June CH. Chimeric Antigen Receptor Therapy for Cancer. Annu Rev Med. 2014;65:333-347.

Chimeric Antigen Receptor T-Cells. http://www.lymphomation.org/programing-t-cells.htm.