Harnessing the Immunotherapy Revolution for the Treatment of Childhood Cancers

• Published in: Cancer cell 2017-04, Vol.31 (4), p.476-485
• Main Authors: Majzner, Robbie G., Heitzeneder, Sabine, Mackall, Crystal L.
• Format: Article
• Language: English
• Subjects: adoptive T cell therapy; Antibodies, Bispecific - pharmacology; Antibodies, Bispecific - therapeutic use; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antigens, CD19 - genetics; Antigens, CD19 - immunology; checkpoint inhibitor; chimeric antigen receptor; Humans; immunotherapy; Immunotherapy - methods; monoclonal antibody; Mutation; Neoplasms - genetics; Neoplasms - therapy; pediatric oncology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - immunology; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Receptors, Antigen - genetics; Receptors, Antigen - immunology; Recombinant Proteins - genetics; Recombinant Proteins - immunology
• ISSN: 1535-6108; 1878-3686
• DOI: 10.1016/j.ccell.2017.03.002

Cancer immunotherapies can be classified into agents that amplify natural immune responses (e.g., checkpoint inhibitors) versus synthetic immunotherapies designed to initiate new responses (e.g., monoclonal antibodies [mAbs], chimeric antigen receptors [CARs]). Checkpoint inhibitors mediate unprecedented benefit in some adult cancers, but have not demonstrated significant activity in pediatric cancers, likely due their paucity of neoantigens. In contrast, synthetic immunotherapies such as mAbs and CAR T cells demonstrate impressive effects against childhood cancers. Intense efforts are underway to enhance the effectiveness of pediatric cancer immunotherapies through improved engineering of synthetic immunotherapies and by combining these with agents designed to amplify immune responses. Cancer immunotherapies can be classified into agents that amplify natural immune responses (e.g., checkpoint inhibitors) versus synthetic immunotherapies designed to initiate new responses (e.g., monoclonal antibodies [mAbs], chimeric antigen receptors [CARs]). Checkpoint inhibitors mediate unprecedented benefit in some adult cancers, but have not demonstrated significant activity in pediatric cancers, likely due their paucity of neoantigens. In contrast, synthetic immunotherapies such as mAbs and CAR T cells demonstrate impressive effects against childhood cancers. Intense efforts are underway to enhance the effectiveness of pediatric cancer immunotherapies through improved engineering of synthetic immunotherapies and by combining these with agents designed to amplify immune responses.