CAR T Cell Therapy

What is Chimeric Antigen Receptor (CAR) T Cell and Gene Therapy?

CAR (Chimeric Antigen Receptor) T cell and gene therapy refers to an innovative treatment that manipulates the patient’s own T cells (immune cells) to attack malignant cancer cells. The T cells come from the patient’s blood and are re-programmed in the lab with a special receptor known as a “chimeric antigen receptor” (CAR). After the CAR receptor is added to a patient’s T cells in the lab, they can be grown in large numbers. When the newly engineered CAR T cells are infused back into the patient, they begin to search for and destroy cancer cells with a specific protein target.

CAR T cancer gene therapy is currently being studied as a treatment for many different cancer types and has been approved for different forms of leukemia and lymphoma.

CAR T Cell Therapy

What successes have there been with CAR T-cell therapy?

Here are 3 recent examples of the potential that adoptive cell immunotherapy brings to cancer treatment.

Childhood acute lymphoblastic leukemia (ALL)
Nearly 3 of every 4 children with leukemia are diagnosed with a type called ALL. Treatment for this form of leukemia has improved greatly over the years, so 90% of children are still alive 5 years after their diagnosis. But in about 600 children and young adults with ALL in the United States every year, treatment doesn’t stop the disease from returning. If this happens, survival time is usually measured in just weeks to months.
In a clinical trial with children and young adults with ALL that had not been stopped by standard treatment, a CAR T-cell therapy called tisagenlecleucel (Kymriah) sent the cancer into remission in 52 of the 63 patients. In 3 out of every 4 patients, the ALL still had not come back after 6 months. Based on the results of this study, in August 2017, the U.S. Food and Drug Administration (FDA) approved tisagenlecleucel to treat children and young adults with recurrent ALL.

Non-Hodgkin lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and is quite aggressive. Many people can be successfully treated with a combination of chemotherapy and rituximab (Rituxan), a targeted therapy. However, these types of lymphomas can sometimes worsen during treatment, called “refractory lymphoma,” or they can come back after treatment, called “recurrent lymphoma.” In these cases, CAR T cells may be an effective treatment option.
A clinical trial used tisagenlecleucel to treat people with DLBCL that had worsened after at least 2 previous treatments. The lymphoma went into remission in 43% of the patients in the study. At 6 months after receiving the CAR T-cell therapy, the lymphoma had still not come back in nearly 80% of the patients.
Another study used a different CAR T-cell therapy to treat refractory lymphoma or recurrent lymphoma. In this study, people had DLBCL, primary mediastinal large B-cell lymphoma (an aggressive form of DLBCL that forms in the chest), or transformed follicular lymphoma (a slow-growing subtype of NHL that has turned into DLBCL). The CAR T-cell therapy in this study was called axicabtagene ciloleucel (Yescarta). The immunotherapy slowed or stopped cancer growth in 82% of the patients, and the cancer completely disappeared in more than half (54%). After nearly 9 months, about 40% of the patients still had no signs of cancer. In October 2017, the FDA approved axicabtagene ciloleucel for the treatment of DLBCL that has not been stopped by 2 or more previous treatments.

Multiple myeloma
Multiple myeloma is a blood cancer that involves the plasma cells in the bone marrow. Plasma cells play an important role in the body’s immune system. Multiple myeloma is an incurable disease, and only about one-half of people live 5 years after a diagnosis.
Results from an early clinical trial presented at the 2017 ASCO Annual Meeting showed that a type of CAR T-cell therapy that targets a biomarker known as B-cell maturation antigen (BCMA) can stop multiple myeloma in its tracks. This study included 35 people with multiple myeloma that had come back after treatment, called relapsed or recurrent, or was resistant to treatment, called refractory. Of those 35, 33 patients (94%) had their multiple myeloma go into remission within 2 months of receiving the BCMA CAR T cells.