Highlights of This Issue

Abstract

To augment existing CAR technology, Wang and colleagues transduced selected CMV-specific human T cells to express both a CD19 CAR and a truncated EGFR, and investigated the effects of restimulating CAR+ T cells through an endogenous CMV-specific T cell receptor. This study has demonstrated that the antitumor activity of CMV/CD19 bispecific T cells can be enhanced as a consequence of proliferation following CMV peptide vaccination. Additionally, the bispecific T cells could be ablated in vivo by anti-EGFR antibody cetuximab. This vaccine boost strategy can be extended to multiple malignancies by transducing various tumor-specific CARs into selected CMV patient T cells.Lapatinib inhibits the tyrosine kinases of both HER1 (EGFR) and HER2, although its clinical use in breast cancer is confined to tumors that overexpress HER2. Leary and colleagues report a study with 2 weeks of lapatinib treatment prior to surgery in newly diagnosed primary breast cancer and show that proliferation (Ki67) was significantly decreased in both HER2-negative and HER2-positive tumors. Among HER2-negative tumors, high HER3 mRNA expression identified Ki67 responders, with a trend for combined increase in levels of HER3/HER2 expression to predict response. HER2-HER3 heterodimers could identify patients with HER2-negative breast cancer that might benefit from lapatinib and merit further investigation.Wide excision of osteosarcoma is necessary to effect successful treatment. Bone morphogenetic protein-2 (BMP-2) could improve bone union following tumor reconstruction but is not currently used due to concerns it may prompt recurrence. Geller and colleagues developed an osteosarcoma model system to more clearly define the effect of both surgical margins and BMP-2 on local recurrence in the context of conventional chemotherapy. Margins greater then 997 μm yielded reliable local control using surgery alone. Single-agent and dual-agent chemotherapy lowered these margins to 36 μm and 12 μm, respectively. The application of BMP-2 did not increase local recurrence rates.The interleukin-11 receptor (IL11R) is an established molecular target in primary bone, tumors (such as osteosarcoma), and in secondary bone metastases (such as prostate cancer). In this study the authors evaluated the IL-11R as a target in preclinical models of leukemia and lymphoma and also validated their findings in human tumors. The results indicate that the IL-11R is a suitable cell surface target for ligand-directed applications against leukemia and lymphoma and that BMTP-11, an IL11R-targeting drug prototype (and its derivatives), have translational potential against this group of malignant diseases.