NYESO-1/LAGE-1s and PRAME are targets for antigen specific T cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine

PLoS One. 2012;7(2):e32165. doi: 10.1371/journal.pone.0032165. Epub 2012 Feb 27.


Background: Chondrosarcoma has no proven systemic option in the metastatic setting. The development of a non-cross-resistant strategy, such as cellular immunotherapy using antigen-specific T cells would be highly desirable. NY-ESO-1 and PRAME are members of the Cancer Testis Antigen (CTA) family that have been identified as promising targets for T cell therapy. LAGE-1 is a cancer testis antigen 90% homologous to NY-ESO-1, sharing the 157-165 A*0201 NY-ESO-1 epitope with its transcript variant, LAGE-1s. A number of CTA's have been induced using 5-Aza-2-Deoxycitabine (5-Aza-dC) in other cancers. We sought to evaluate the feasibility of targeting chondrosarcoma tumors using NY-ESO-1/LAGE-1s and PRAME specific T cells using 5-Aza-dC to induce antigen expression.

Methods: We used 11 flash frozen tumors from the University of Washington tumor bank to test for the expression of NY-ESO-1, PRAME, LAGE-1s and LAGE-1L in chondrosarcoma tumors. Using four chondrosarcoma cell lines we tested the expression of these CTA's with and without 5-Aza-dC treatments. Finally, using NY-ESO-1/LAGE-1s and PRAME specific effectors that we generated from sarcoma patients, we evaluated the ability of these T cells to lyse A*0201 expressing chondrosarcoma cell lines in vitro both with and without 5-Aza-dC treatment.

Results: A minority (36%) of chondrosarcoma tumors expressed either NY-ESO-1 or LAGE-1s at >10% of our reference value and none expressed PRAME at that level. However, in all four of the chondrosarcoma cell lines tested, NY-ESO-1 and PRAME expression could be induced following treatment with 5-Aza-dC including in cell lines where expression was absent or barely detectable. Furthermore, NY-ESO-1/LAGE-1s and PRAME specific CD8+ effector T cells were able to specifically recognize and lyse A*0201 expressing chondrosarcoma cell lines following 5-Aza-dC treatment.

Conclusion: These data suggest that adoptive immunotherapy in combination with 5-Aza-dC may be a potential strategy to treat unresectable or metastatic chondrosarcoma patients where no proven systemic therapies exist.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / chemistry
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / chemistry*
  • Antigens, Surface / chemistry*
  • Antimetabolites, Antineoplastic / pharmacology*
  • Azacitidine / pharmacology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Chondrosarcoma / drug therapy
  • Chondrosarcoma / immunology*
  • Chondrosarcoma / metabolism
  • DNA Primers / chemistry
  • Epitopes / chemistry
  • HLA Antigens
  • Humans
  • Immunophenotyping
  • Immunotherapy / methods
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Male
  • Membrane Proteins / chemistry
  • Peptides / chemistry
  • Real-Time Polymerase Chain Reaction
  • Testis / metabolism


  • Antigens
  • Antigens, Neoplasm
  • Antigens, Surface
  • Antimetabolites, Antineoplastic
  • CTAG1B protein, human
  • CTAG2 protein, human
  • DNA Primers
  • Epitopes
  • HLA Antigens
  • Interleukin-2 Receptor alpha Subunit
  • Membrane Proteins
  • PRAME protein, human
  • Peptides
  • Azacitidine