Image Credit: Blausen.com staff (2014). “Medical gallery of Blausen Medical 2014”. WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436.

The Science Behind CAR T-Cell Therapy

Though it’s true that, in some cases, our bodies can spontaneously and furiously turn against us, they are also purposefully hard-wired to guard us against ourselves. Did you know that your own body is one of the best defenses against most ailments and diseases, especially when it comes to cancer? In scientific terms, this is referred to as immunotherapy, and the word indicates using your immune system to treat you. Over the past several years, immunotherapy has been used to harness a patient’s immune system to attack cancer.

Racing the front line of immunotherapy is Chimeric Antigen Receptor T-Cell Therapy, otherwise known as CAR T-Cell Therapy. That may seem like a mouthful of a name for a potential superhero cell that gets recruited into the immunotherapy army right from your own body “marrows.” The term chimeric means something new formed  from “parts.” T cells are a type of white blood cell part of the immune system and develop from stem cells in the bone marrow. They help protect the body from infection and may help fight cancer. T cells are taken from a patient’s blood in this cancer treatment. These cells are genetically modified to express a protein that recognizes and binds to a target called CD19, found on cancerous B cells. These new chimeric patient T-cells are grown in a lab to produce large numbers of newly engineered patient cells. The cells are then injected into the patient like well-trained cancer-fighting ninjas that will hopefully multiply and conquer inside your body. When the reprogrammed T cells are back in the patient, they flow throughout the body and begin locating cancerous B cells. Your body welcomes and recognizes the new cells as “living drugs” that will hunt and find the specific cancer they target.

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CAR T-Cell Compared to Traditional Treatments

If CAR T-Cell therapy sounds like a new uncharted genetic innovation, it’s most definitely not. You can rest assured that scientists have studied this type of cell manipulation for decades. Many people might not realize that this innovative therapy is the culmination of more than sixty years of dedicated research utilizing knowledge of the immune system, genetic engineering, antibody therapy, and a deep understanding of the underpinnings of blood cancers. In the 1950s, understanding the procedure known as bone marrow transplantation aided the groundwork for developing this therapy. This was the first concept of infusing cells into blood cancer patients to control cancer and understanding that T cells have the power to kill cancer cells.

Several years of dedicated research led to the first CAR T-cell therapy, tisagenlecleucel-T (Kymriah™), getting approval from the U.S. Food and Drug Administration (FDA) on August 30, 2017, for the treatment of children and young adults 25 and younger with relapsed and refractory acute lymphoblastic leukemia (ALL). Since 2017, six CAR T-cell therapies have been approved by the Food and Drug Administration (FDA). All are approved to treat blood cancers, including lymphomas, some forms of leukemia, and, most recently, multiple myeloma. This therapy has proven effective in clinical trials, and tens of thousands of people have received CAR-T cell treatment. Many adults and children near death are now in remission, and some remain healthy more than five years after treatment.

So how do traditional chemotherapy and radiation compare? The initial development of CAR T-cell therapies focuses on the most common cancer in children, acute lymphoblastic leukemia (ALL). More than 80% of children diagnosed with ALL that arises in B cells, the predominant type of pediatric ALL, will be cured by intensive chemotherapy. But effective treatments have been limited for patients whose cancers return or relapse after chemotherapy or a stem-cell transplant.CAR T-cell therapy is approved to treat children and adolescents with fairly advanced B cell acute lymphoblastic leukemia (ALL), but not other leukemias or pediatric cancers. CAR T-cell therapy is an option for patients who have very resistant ALL. Cancer has come back once, but they can’t have a stem cell transplant because they aren’t well enough or don’t have a donor. Roughly 85% of ALL patients are treated very successfully with standard chemotherapy. For the remaining 15% of cases, representing many children in the United States, chemotherapy is reported as only working temporarily or not. CART T-cell therapy is not usually prescribed for newly diagnosed leukemia but only for patients whose leukemia is not responding to chemotherapy and whose disease has come back after a bone marrow transplant.

Cancer Families Should Know

The great news is that research on CAR T-cell therapy for a broader range of pediatric cancers at different treatment levels has continued. There are currently hundreds of ongoing clinical trials (mainly adult). Part of this expansion is a product of researchers having identified additional markers on cancer tumor cells that might be good targets for CAR T-cells. However, you should understand a few things about this immunotherapy and its accessibility when doing your own research on options for your child. According to medical and scientific experts in CAR t-cell therapy, four key issues make developing CAR T-cell therapies for pediatric indications a unique challenge.

Firstly, cancers in children don’t always act or respond to therapy the same way as in adults. In addition, the spectrum of malignancies that affect children is unique, and some are rarely seen in adults. For example, children with cancer often have aggressive diseases with more challenging characteristics. Second, since the pediatric population needing treatment for some cancers is so small, it is challenging to get pharmaceutical companies to invest in technologies for pediatric malignancies. A third challenge is that CAR T-cell therapies are labor-intensive and take a long time to develop in research and subsequent manufacturing. The same cancer therapy designed for adults may not necessarily be used for children. Finally, a lack of target antigens (markers) can hinder the development of CAR T-cell therapy for children. However, despite the challenges, including a lack of economic incentives, several clinical trials are examining CAR T-cell therapies for pediatric cancers.

To learn more about some of the current pediatric cancer trials using CAR T-cell therapy, check out the studies below:

• City of Hope: Investigational CD123-directed CAR T-cell therapy for patients older than 12 years who have relapsed or refractory acute myeloid leukemia or persistent/recurrent blastic plasmacytoid dendritic cell neoplasm. Clinical Trial #: NCT02159495
• Novartis Pharmaceuticals: Examining CAR T-cell therapy as a potential solution to the problem of persistent minimal residual disease (MRD) after front-line chemotherapy. Clinical Trial #: NCT03876769
• Novartis Pharmaceuticals: evaluating CAR T-cell therapy for children with high-risk relapsed or refractory B-cell non-Hodgkin lymphoma who have poor survival and overall response rates after conventional salvage chemotherapy. Clinical Trial #: NCT03610724
• National Cancer Institute (NCI): evaluating a CD22-directed CAR T-cell therapy as second-line treatment for children and young adults with relapsed or refractory B-cell malignancies. Clinical Trial # NCT02315612

If you or a friend or loved one has had a child recently diagnosed with cancer, please reach out to Here to Serve for help. Here to Serve provides practical wrap-around support to families who have a child or parent of a child(ren) diagnosed with cancer. Here to Serve is here to help!

By Sameera Rangwala, M.S., M.P.H

About the Author

Sameera Rangwala spent 15 years in the biotechnology industry. As a scientist and research professional, she uses her skills to blog and provides words of support to the cancer community.

This publication is for informational purposes only. Always seek the advice of a physician or other qualified healthcare provider with any questions regarding a medical condition and appropriate treatment.