Genetically Modified T cells Targeting Interleukin-11 Receptor α-Chain Kill Human Osteosarcoma Cells and Induce the Regression of Established Osteosarcoma Lung Metastases

The treatment of osteosarcoma pulmonary metastases remains a challenge. T cells genetically modified to express a chimeric antigen receptor (CAR), which recognizes a tumor-associated antigen, have shown activity against hematopoietic malignancies in clinical trials, but this requires the identification of a specific receptor on the tumor cell. In the current study, we found that interleukin (IL)-11R alpha was selectively expressed on 14 of 16 osteosarcoma patients' lung metastases and four different human osteosarcoma cell lines, indicating that IL-11R alpha may be a novel target for CAR-specific T-cell therapy. IL-11R alpha expression was absent or low in normal organ tissues, with the exception of the gastrointestinal tract. IL-11R alpha-CAR-specific T cells were obtained by non-viral gene transfer of Sleeping Beauty DNA plasmids and selectively expanded ex vivo using artificial antigen-presenting cells derived from IL-11R alpha + K562 cells genetically modified to coexpress T-cell costimulatory molecules. IL-11R alpha-CAR(+) T cells killed all four osteosarcoma cell lines in vitro; cytotoxicity correlated with the level of IL-11R alpha expression on the tumor cells. Intravenous injection of IL-11R alpha-CAR(+) T cells into mice resulted in the regression of osteosarcoma pulmonary metastases with no organ toxicity. Together, the data suggest that IL-11R alpha-CAR T cells may represent a new therapy for patients with osteosarcoma pulmonary metastases. Cancer Res; 72(1); 271-81. (C) 2011 AACR.