Genetically modified T cells targeting interleukin-11 receptor α-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases

Gangxiong Huang, Ling Yu, Laurence J.N. Cooper, Mario Hollomon, Helen Huls, Eugenie S. Kleinerman

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)271-281
Number of pages11
JournalCancer Research
Volume72
Issue number1
DOIs
StatePublished - Jan 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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