What’s New in Immunotherapy?
Checkpoint Inhibitors for Pediatric Cancer
Instead of relying solely on outside interventions such as surgery, chemotherapy, and radiation therapy, immunotherapy empowers the body’s natural immune system to recognize, target, and destroy cancer cells. It’s a safe bet that if you have a child with a cancer diagnosis, you’ve been searching every corner of the earth for the best and most advanced treatment for your child.
In past blogs, we’ve discussed new therapies like Chimeric Antigen Receptor T-Cell Therapy, which has shown great promise as a treatment option for pediatric cancer, especially for relapsed or refractory acute lymphoblastic leukemia (ALL). When they work, immunotherapies are a type of cancer treatment that harnesses the power of a person’s immune system to fight cancer cells.
Immunotherapy is highly specific, explicitly targeting cancer cells while sparing healthy cells. Unlike some traditional cancer treatments such as chemotherapy, immunotherapies could be advantageous because they do not cause damage to healthy cells in the body, making them a potentially less toxic option for pediatric patients.
The “new kid on the block” in pediatric immunotherapies are called Immune Checkpoint Inhibitors (ICIs). As a quick refresher, remember that we all have T-cells, a.k.a T lymphocytes. They are a type of white blood cell that plays a crucial role in the immune system. T-cells are responsible for recognizing and attacking foreign substances, such as viruses or bacteria, as well as cancer cells and other abnormal cells in the body. T-cells can recognize these foreign substances by their unique surface markers, called antigens, and can then mount a targeted immune response to eliminate the threat.
Why would we need them?
Our bodies all have checkpoint proteins within them. These proteins normally act as brakes on T- cells, preventing them from attacking healthy cells in the body. However, some cancer cells can produce proteins that interact with checkpoint proteins on T-cells, essentially telling the immune system to leave them alone. So cancer cells can sometimes confuse our T-cells into letting their guard down while trying to protect the body from cancer itself.
How do they work?
Cancer cells can use immune checkpoints to evade the immune system and avoid destruction. Checkpoint inhibitors are a type of immunotherapy that works by blocking certain proteins on the surface of immune cells that inhibit immune response against cancer cells. The PD-1 pathway, also known as the programmed cell death 1 pathway, is a mechanism that helps regulate the immune system and prevent the body’s immune cells from attacking healthy tissues. The pathway involves interactions between proteins on the surface of immune cells, such as T-cells, and proteins on the surface of other cells in the body, such as cancer cells or normal cells.
When activated, the PD-1 pathway sends signals to the immune cells to reduce their activity and prevent them from attacking healthy tissues. This can be beneficial in preventing autoimmune diseases, but it can also be harmful in preventing the immune system from attacking cancer cells or other abnormal cells in the body. As mentioned, certain cancers and viruses can take advantage of the PD-1 pathway to evade the immune system. They do this by producing proteins, such as PD-L1, that interact with the PD-1 protein on immune cells, effectively “turning off” the immune response and allowing cancer or virus to grow and spread.
Source Reference: https://iqbiosciences.com/
Status for Pediatric Cancer
- The use of immune checkpoint inhibitors to treat pediatric cancers is still developing, as these therapies enhance T-cell responses to fight tumors that have been suppressed by inhibitory pathways.
- Although ICIs have shown success in treating adult cancers, initial clinical trials using single-agent ICIs to treat a variety of pediatric cancers have been underwhelming, with few responses observed, except in pediatric classic Hodgkin lymphoma cases. This may be due to differences in the immunogenicity of childhood cancers compared to adult cancers, as pediatric cancers generally have fewer neoantigens (a new protein that forms on cancer cells when certain mutations occur in tumor DNA). Fortunately, there is renewed optimism that certain groups of children with cancer could experience positive outcomes through the use of ICI therapies.
- The U.S. Food and Drug Administration (FDA) has approved some checkpoint inhibitors for treating specific types of pediatric cancers. However, ongoing clinical trials are necessary to gather additional safety and efficacy data before these medications can be more widely used in children with other types of cancer not mentioned below.
- Pembrolizumab (Keytruda) -approved for adults and children aged 12 or older who have undergone surgery to remove stage IIB, stage IIC, or stage III melanoma and cancerous lymph nodes, and aims to reduce the risk of melanoma recurrence.
- Nivolumab (Opdivo)– approved for the treatment of colorectal cancer in both adults and children aged 12 years and older. It is specifically used to treat microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) cancer that has spread to other parts of the body and has worsened despite previous treatment with fluoropyrimidine, oxaliplatin, and irinotecan hydrochloride (chemotherapy medications).
- Atezolizumab (Tecentriq) -approved treatment option for alveolar soft part sarcoma that has either spread to other parts of the body or cannot be removed through surgery. In both adults and children aged 2 years and older, atezolizumab can be used alone or in combination with other drugs as part of the treatment plan.
It’s important to remember that checkpoint inhibitors are only approved for certain types of pediatric cancer and specific patient populations. However, there is ongoing research in this area, and new treatments and indications may be approved in the future. To learn more about FDA-approved medications for childhood cancer, please visit the National Cancer Institute’s website at https://www.cancer.gov/about-cancer/treatment/drugs/cancer-type.
- The National Cancer Institute (NCI) offers a great website that you might find helpful! It provides a searchable database of clinical trials for pediatric cancer, along with information on how to enroll in a trial and what the process looks like. Additionally, the site includes resources for families and healthcare providers who want to learn more about pediatric cancer clinical trials. The website is called “Pediatric Treatment Editorial Board (PTEB) – Clinical Trials” and it can be accessed at https://www.cancer.gov/about-cancer/treatment/clinical-trials/pediatric-treatment-editorial-board.
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By Sameera Rangwala, M.S., M.P.H
About the Author
Sameera Rangwala spent over 15 years in the biotechnology industry and is currently a life science educator for children in grades 5-8. As a scientist and research professional, she uses her skills to blog and provides words of support to the cancer community.
All content in this blog is for informational and educational purposes only. Always consult a medical provider in your particular area of need before making significant changes in your medical decisions or lifestyle.