Cells are being created continuously in our bodies. Both good and bad cells. In the past century, many factors such as use of pesticides and other toxins have weakened our immune system. Our immune system is designed to seek out and destroy cancer cells, thus, creating an environment where our natural immune system cannot control the growth of cancer cells in the body. Cancer tumors begin when more cancer cells are being created faster than our immune system can destroy. (See https://www.cancer.gov/types/childhood-cancers and oncosec.com/cancer-escape-immune-system.)
Overcoming cancer is a process of reversing the conditions that allowed the cancer to develop, as well as going after and killing the cancerous cells. Today, highly toxic treatments are used to kill these cancer cells. For example, traditional chemotherapies target rapidly dividing cells in the body, both tumor cells and healthy, normal cells. Radiation therapies target cells in a specific region but damage all other cells in the path of the radiation beam. In other words, the good cells that we need like bone marrow, reproductive systems, hair follicles are killed along with the bad cancer cells.
Although there have been tremendous advances in the treatment of childhood cancers, some therapies can cause health problems that occur months or years after a disease is diagnosed or after treatment has ended. An alternative, more natural, less toxic approach is to strengthen the depleted immune system and build the immune system faster than the cancer cells can multiply.
Immunotherapy, also called biological therapy, is a type of cancer treatment designed to use the body’s natural defenses to fight the cancer. It uses materials either made by the body or in a laboratory from natural material, to enhance, target, or restore immune system function. Research is still needed to demonstrate how immunotherapy treats cancer, especially pediatric cancer. (See www.cancercenter.com/how-ctca-treats-cancer)
More specifically, immuno-oncology is a type of immunotherapy that has the specific purpose of treating cancer (https://www.immunooncology.bmsinformation.com/how-io-is-different). Immunotherapies fall into five general categories: checkpoint inhibitors, which disrupt signals that allow cancer cells to hide from an immune attack; cytokines, protein molecules of the immune system that help regulate and direct its actions; cancer vaccines, short RNA, antibodies or protein molecules that instruct the immune system about features that differentiate the tumor from the healthy normal body; adoptive cell, which removes immune cells from the patient and attempts to selectively train and grow them in the lab before re-infusing them in the patient for a stronger response than cancer vaccines; and CAR-T, in which T-cells of the immune system are engineered to replace the inherent T-cell receptor with a Chimeric Antigen Receptor (CAR) that can selectively target tumor cells and mount an immune response against them.
Childhood immunotherapy is still at the very early stages of research. Many immunotherapies are being studied in clinical trials as we write. The following are examples of FDA-approved immunotherapies currently under investigation:.
- Tisagenlecleucel (Kymriah™), a type of immunotherapy called CAR T-cell therapy, for some children and young adults with advanced acute lymphoblastic leukemia (ALL).
- Dinutuximab (anti-GD2 antibody) immunotherapy for neuroblastoma.
- In an early-phase clinical trial of a new oral drug, selumetinib, children with the common genetic disorder neurofibromatosis type 1 (NF1) and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage.
See https://www.cancer.gov/types/childhood-cancers/research for more about these clinical trials.
Our immunotherapy work at Treehouse focuses on the identification of molecules that can help our immune system distinguish cancer cells from normal cells. Treehouse research looks for particular types of such molecules called neoepitopes. Neoepitopes are abnormal protein pieces that are formed by the cancer cells when there are changes to the normal protein sequence as a result of DNA mutations. Neoepitopes can be displayed on the surface of cancer cells and can then be recognized by the immune system to elicit an immune response. Childhood cancers have fewer mutations than adult cancers, and hence tend to have fewer neoepitopes than adult cancers. However, there are exceptions to this general phenomenon. Our immunotherapy work identifies pediatric tumors where immunogenic neoepitopes exist and can be harnessed to enhance the immune response. For example, in a recent study we found a particular neoepitope that can form in neuroblastoma patients as a result of the mutations in ALK gene.
By studying cancer at a molecular level using data science Treehouse hopes to learn how clinicians can help patients harness the body’s natural defenses to fight cancer.