Pediatric
sarcomas are a heterogeneous group of malignant
tumors of bone and soft tissue origin. Although more than 100 different histologic subtypes have been described, the majority of pediatric cases belong to the Ewing's family of
tumors,
rhabdomyosarcoma and
osteosarcoma. Most patients that present with localized stage are curable with surgery and/or
chemotherapy; however, those with metastatic disease at diagnosis or those who experience a relapse continue to have a very poor prognosis. New
therapies for these patients are urgently needed.
Immunotherapy is an established treatment modality for both liquid and solid
tumors, and in pediatrics, most notably for
neuroblastoma and
osteosarcoma. In the past,
immunomodulatory agents such as
interferon,
interleukin-2, and liposomal-muramyl tripeptide phosphatidyl-
ethanolamine have been tried, with some activity seen in subsets of patients; additionally, various
cancer vaccines have been studied with possible benefit.
Monoclonal antibody therapies against
tumor antigens such as disialoganglioside GD2 or immune checkpoint targets such as CTLA-4 and PD-1 are being actively explored in pediatric
sarcomas. Building on the success of adoptive T cell
therapy for EBV-related
lymphoma, strategies to redirect T cells using
chimeric antigen receptors and
bispecific antibodies are rapidly evolving with potential for the treatment of
sarcomas. This review will focus on recent preclinical and clinical developments in targeted agents for pediatric
sarcomas with emphasis on the immunobiology of immune checkpoints, immunoediting, tumor microenvironment, antibody engineering, cell engineering, and
tumor vaccines. The future integration of antibody-based and cell-based
therapies into an overall treatment strategy of
sarcoma will be discussed.