Tumor immunotherapy in pediatric oncology

Background: The importance of immunotherapy for children and adolescents with cancer is increasing, but their applicability is somewhat different compared to their use in adult cancer patients. Aim: Immunotherapy approaches and their perspectives in pediatric oncology are discussed. Methods: This manuscript is based on a literature search in PubMed related to the topic of immunotherapy in pediatric oncology. Results: The backbone of cancer immunotherapy is the use of monoclonal antibodies and conjugates, which are today standard of care for the treatment of leukemia, lymphoma and neuroblastoma. Their highly specific antigen binding characteristics allowed for the development of bispecific antibodies and chimeric antigen receptors, which have shown clinical efficacy in B‑precursor leukemia. In contrast to treatment of adults with cancer, the relatively new principle of inhibition of negative immune regulation by immune checkpoint blockade has not become established in pediatric oncology, due to the absence of a pre-existing anti-tumor immune response in most pediatric oncology cases. This may be due, among other things, to a 14-fold lower frequency of somatic mutations on average in pediatric cancers, which leads to a lower level of neoantigen formation. Conclusion: The future of immune checkpoint blockade may lie in combination therapies that induce an increase of anti-tumor effector cells and concomitant inhibition of immune suppressive signals in the tumor microenvironment. The steady increase of novel constructs and innovative combinations raise expectations for additional effective future immunotherapeutics for children with cancer.