Antibody-based targeted radiation to pediatric tumors

Abstract

Radioimmunotherapy (RIT) for pediatric tumors remains in its infancy despite its potential as an attractive therapeutic modality. Most childhood tumors are radiation sensitive, but the side effects of external beam radiation are well recognized. Despite achieving complete remissions with sophisticated combination therapies, treatment failure primarily results from the inability to eradicate minimal residual disease, which is typically distant and occult. RIT can conceivably target such disease and improve cancer treatment. Because intensive chemotherapy regimens used in most childhood cancers are highly immunosuppressive, repeated administration of radiolabeled monoclonal antibodies is possible without the immediate induction of human antimouse or human antichimeric antibody responses. Despite the differences in biology between childhood and adult hematologic malignancies, they share several tumor antigens for which RIT agents are now available. However, safety and efficacy profiles in children remain to be defined. On the other hand, the antigen repertoire of pediatric solid tumors differs substantially from that in adults, partly because of differing lineages: pediatric solid tumors are typically of embryonal origin, whereas adult tumors are usually carcinomas of epithelial origin. Hence, RIT agents licensed for adult tumors are generally not applicable to pediatric solid tumors. Tumor-selective radioimmunoconjugates specific for embryonal tumors of childhood are currently being actively investigated. Without substantial policy changes in drug development for orphan indications, however, these agents are not likely to be widely available in the near future.