Immunotherapy is the process of using a component, or components, of the immune system to eliminate cancer.
One of the earliest observations that immunotherapy could be beneficial in pediatric oncology came from William Coley, a surgeon who practiced from 1890-1936. While taking care of patients with Ewing sarcoma, the 2nd most common bone tumor in children, he observed a patient who had a bad Strep infection call erysipelas develop spontaneous remission of his tumor. He began producing crude bacterial extracts that were eventually termed “Coley toxins” to treat patients with sarcoma, but because he could not reproduce the results and standardize production of the toxins, the practice fell out of favor. We now know that likely the Coley toxins stimulated toll-like receptors, which are our bodies’ natural way of detecting bacteria, viruses and protozoa, causing immune cells to become activated and eliminate the sarcoma. In fact, other toll-like receptor stimulators are now FDA-approved to treat bladder cancer (BCG-CWS) and basal cell skin cancer (Imiquimod) as well as prevent cervical cancer (the HPV vaccine has aluminum salts, which stimulate toll-like receptor 4).
Because of advancements in genetic engineering and in culturing cells, we can now produce more sophisticated immunotherapies that are more specific for pediatric cancer. At UW, research by Dr. Paul Sondel contributed toward the development of a monoclonal antibody against neuroblastoma, the most common solid tumor in children outside of the brain. This antibody, called ch14.18, binds to neuroblastoma and makes it a target by natural killer (NK) cells for destruction. By doing so, in phase III trials we have observed an improvement in survival in children with stage IV neuroblastoma, the most advanced form of the cancer. United Therapeutics has recently obtained orphan drug designation to develop ch14.18 on a commercial scale for FDA approval. Other antibodies are also being tested, like the immunocytokine hu14.18-IL2.
Dr. Ken DeSantes has also been infusing NK cells from the parents of children undergoing haploidentical peripheral blood stem cell transplant to treat leukemias and solid tumors. Natural killer (NK) cells are an important component of our body’s immune system responsible for controlling both virally-infected cells and tumors. NK cells also support white blood cell development.
He has designed a novel pilot trial where NK cells isolated from haploidentical donors (most often the child’s mother or father) are infused to children with refractory or relapsed cancer right after a reduced intensity peripheral blood stem cell transplant. The donor of the stem cells is the same as the NK cell donor.
We believe giving NK cells in this fashion serves several important purposes:
- Because NK cells are inactivated when they encounter “self” molecules (autologous), by using NK cells from a parent (allogeneic), we insure those NK cells will be mismatched to the patient’s tumor, and therefore be better able to attack and kill it.
- The immunologic environment present after a stem cell transplant is highly conducive to NK cell expansion because of the presence of supporting growth factors.
- Because NK cells support white blood cell development, theoretically they could enhance stem cell engraftment and immune reconstitution.
- Using a reduced intensity conditioning (chemotherapy) regimen to prep the patient for transplant reduces the risk of organ toxicity to children who are already heavily pretreated from their initial chemotherapy regimen.
In 2013, UW was selected as one of 7 children’s hospitals as part of a Pediatric Cancer Dream Team. The goal of this team is to (1) genetically sequence pediatric cancers to look for new targets that can be recognized by the immune system, and (2) to develop novel immunotherapies against these targets for the clinic. Along with Drs. Sondel and DeSantes, Dr. Christian Capitini and Dr. Mario Otto are pursuing translational research in immunotherapy as part of this award.
We are also one of 27 member centers of the Cancer Immunotherapy Trials Network through the National Cancer Institute.
To hear more about immunotherapy, please refer to the following video and podcast: