L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice

• DOI: 10.1371/journal.pone.0146885
• Publication Date: 2016-01-13T18:38:42Z
• Authors: Hao Hong; Christine E. Brown; Julie R. Ostberg; Saul J. Priceman; Wen-Chung Chang; Lihong Weng; Paul Lin; Mark T. Wakabayashi; Michael C. Jensen; Stephen J. Forman
• Keywords: Adoptive Cell Transfer

New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated impressive potential of adoptive therapy using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved solid cancers. We sought determine whether genetically-modified targeting CE7-epitope L1-CAM, cell adhesion molecule aberrantly expressed in several promise as an immunotherapy first demonstrating that L1-CAM was highly over-expressed on panel cancer lines, primary tumor tissue specimens, ascites-derived cells. Human central memory derived (TCM) were then genetically modified express anti-L1-CAM CAR (CE7R), which directed effector function upon stimulation assessed by vitro cytokine secretion cytotoxicity assays. also found CE7R+ able Intraperitoneal (i.p.) administration TCM induced significant regression i.p. established SK-OV-3 xenograft tumors mice, inhibited ascites formation, conferred survival advantage compared with control-treated animals. Taken together, these indicate transfer L1-CAM-specific offer novel effective strategy advanced cancer.