Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Pharmacol Ther. 2021 Jul;223:107892. doi: 10.1016/j.pharmthera.2021.107892. Epub 2021 May 14.
Cancer immunotherapies have revolutionized how we can treat adult malignancies and are being translated to pediatric oncology. Chimeric antigen receptor T-cell therapy and bispecific antibodies targeting CD19 have shown success for the treatment of pediatric patients with B-cell acute lymphoblastic leukemia. Anti-GD2 monoclonal antibody has demonstrated efficacy in neuroblastoma. In this review, we summarize the immunotherapeutic agents that have been approved for treating childhood cancers and provide an updated review of molecules expressed by pediatric cancers that are under study or are emerging candidates for future immunotherapies. Advances in our knowledge of tumor immunology and in genome profiling of cancers has led to the identification of new tumor-specific/associated antigens. While cell surface antigens are normally targeted in a major histocompatibility complex (MHC)-independent manner using antibody-based therapies, intracellular antigens are normally targeted with MHC-dependent T cell therapies. Glypican 2 (GPC2) and B7-H3 (CD276) are two cell surface antigens that are expressed by a variety of pediatric tumors such as neuroblastoma and potentially can have a positive impact on the treatment of pediatric cancers in the clinic.
癌症免疫疗法彻底改变了我们治疗成人恶性肿瘤的方式，目前正在向儿科肿瘤学领域转化。嵌合抗原受体 T 细胞疗法和针对 CD19 的双特异性抗体在治疗儿童 B 细胞急性淋巴细胞白血病方面已取得成功。抗 GD2 单克隆抗体在神经母细胞瘤中显示出疗效。在这篇综述中，我们总结了已批准用于治疗儿童癌症的免疫治疗药物，并提供了正在研究或可能成为未来免疫治疗新兴候选药物的儿科癌症表达分子的最新综述。我们对肿瘤免疫学的认识以及对癌症的基因组分析的进展，导致了新的肿瘤特异性/相关抗原的鉴定。虽然细胞表面抗原通常通过基于抗体的疗法在主要组织相容性复合体 (MHC) 非依赖性方式进行靶向，但细胞内抗原通常通过 MHC 依赖性 T 细胞疗法进行靶向。Glypican 2 (GPC2) 和 B7-H3 (CD276) 是两种细胞表面抗原，它们在神经母细胞瘤等多种儿科肿瘤中表达，并且可能对儿科癌症的临床治疗产生积极影响。
