Highlights of This Issue

Abstract

The cell-surface immunomodulatory protein B7-H3 is upregulated in a large proportion of human cancers. From a panel of B7-H3 monoclonal antibodies (mAb) generated via intact cell-based immunizations, Loo and colleagues selected a mAb displaying exquisite tumor/normal differential binding. MGA271, the resulting engineered anti–B7-H3 mAb, mediated potent antibody-dependent cellular cytotoxicity against a range of tumor types and showed potent antitumor activity toward tumor xenografts. The enhanced antitumor activity and favorable safety profile support initiation of a clinical study of MGA271 in patients with B7-H3-positive metastatic or recurrent adenocarcinoma.Tumor-infiltrating macrophages are potential independent indicators of poor outcome in classical Hodgkin lymphoma (cHL) in adults, but nothing is known in pediatric cases. In this study, Barros and colleagues investigated macrophages and dendritic cells in pediatric cHL, taking into account the Epstein–Barr virus (EBV) status of the Hodgkin and Reed–Sternberg cells and lymphocyte composition of the tumor microenvironment. The results show that macrophage composition in pediatric cHL is distinct from that of adult cHL and that the prognostic role of macrophages in pediatric cHL is affected by EBV status.Wong and colleagues performed a retrospective pharmacokinetic–pharmacodynamic analysis of xenograft/allograft efficacy data for 8 anticancer agents to investigate whether these preclinical models are predictive of clinical response. Tumor growth inhibition (TGI) was significantly correlated with clinical response only following simulation of TGI at clinically relevant exposures. Agents that led to greater than 60% TGI in preclinical models, at clinically relevant exposures, were more likely to lead to a clinical response. This study provides a framework for the successful use of murine subcutaneous tumor models to select active agents for further clinical evaluation.Madic and colleagues describe the validation in clinical samples of the pyrophosphorolysis-activated polymerization method to measure circulating tumor DNA (ctDNA) with a 1-copy sensitivity. ctDNA was shown in 20 of 21 patients with metastatic uveal melanoma in amounts correlated with the tumor burden. This technique, which is based on the detection of single-nucleotide mutations, is simple and inexpensive and could be implemented in any clinical molecular biology laboratory. The technique could also be applied to any tumor type with recurrent activating mutations, such as KRAS, BRAF, or PI3K.