title: Genetically modified T cells targeting interleukin-11 receptor α-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases.
abstract: 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)-11Rα was selectively expressed on 14 of 16 osteosarcoma patients' lung metastases and four different human osteosarcoma cell lines, indicating that IL-11Rα may be a novel target for CAR-specific T-cell therapy. IL-11Rα expression was absent or low in normal organ tissues, with the exception of the gastrointestinal tract. IL-11Rα-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-11Rα + K562 cells genetically modified to coexpress T-cell costimulatory molecules. IL-11Rα-CAR(+) T cells killed all four osteosarcoma cell lines in vitro; cytotoxicity correlated with the level of IL-11Rα expression on the tumor cells. Intravenous injection of IL-11Rα-CAR(+) T cells into mice resulted in the regression of osteosarcoma pulmonary metastases with no organ toxicity. Together, the data suggest that IL-11Rα-CAR T cells may represent a new therapy for patients with osteosarcoma pulmonary metastases.
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Gangxiong
authors.initials: G
authors.lastname: Huang
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Laurence Jn
authors.initials: LJ
authors.lastname: Cooper
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Mario
authors.initials: M
authors.lastname: Hollomon
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Helen
authors.initials: H
authors.lastname: Huls
authors.affiliation: Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.
authors.forename: Eugenie S
authors.initials: ES
authors.lastname: Kleinerman
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018274:Electroporation; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053703:Interleukin-11 Receptor alpha Subunit / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000473:pathology*; D010957:Plasmids; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: C508428:IL11RA protein, human; D053703:Interleukin-11 Receptor alpha Subunit
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