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.
Highlights
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
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 restrictedT 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 have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer
Summary
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. CD19 CD19 is an ideal immune target, being universally expressed by acute lymphoblastic leukemia, the most common malignancy of children, whereas expression on non-tumor tissues is restricted to B-cells and their progenitors but not hematopoietic stem cells (Nadler et al, 1983, 1984) Despite this favorable tissue distribution, early studies with unconjugated anti-CD19 monoclonal antibodies and anti-CD19 immunotoxins against CD19+ lymphomas were ineffective (Stone et al, 1996; Furman et al, 2011; Schindler et al, 2011). Moxetumomab pasudotox, a high-affinity anti-CD22 antibody conjugated to pseudomonas exotoxin, has induced complete responses in 4/17 (24%) patients with refractory and relapsed pediatric ALL and most patients showed evidence for antitumor activity with little toxicity (Wayne et al, 2010; NCT00659425) Inotuzumab ozogamycin is another anti-CD22 immunotoxin under study in patients 16 years of age and older with ALL and B-cell lymphoma (NCT01134575). Anti-CD22 CAR T cell therapy is being actively pursued with some preclinical activity reported (James et al, 2008)
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