Immunotherapy targets in pediatric cancer

Abstract

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

Keywords: adoptive immunotherapy; antibody therapy; chimeric antigen receptor; immunotherapy; pediatric cancer; tumor antigens; tumor immunity.

Figure 1

Chimeric antigen receptors provide for expanded targeting opportunities compared to T cell receptors. Chimeric antigen receptors (CARs) combine a variety of antigen-recognition strategies with the functionality of the T cell receptor and a co-stimulatory signal (i.e., Signal 2) and eliminates MHC restriction. This potentially allows for the targeting of any extracellular moiety such as signaling or cytokine receptors, cell adhesion molecules, gangliosides, or other proteins communicating with the extracellular matrix. In contrast, the classic T cell receptor recognizes processed peptides in the context of MHC providing a strategy for targeting intracellular, immunogenic antigens.