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

Seth M. Pollack, Yonqing Li, Megan J. Blaisdell, Erik A. Farrar, Jeffrey Chou, Benjamin L. Hoch, Elizabeth T. Loggers, Eve Rodler, Janet F. Eary, Ernest U. Conrad, Robin L. Jones, Cassian Yee

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numbere32165
JournalPLoS One
Volume7
Issue number2
DOIs
StatePublished - Feb 27 2012
Externally publishedYes

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Chondrosarcoma
T-cells
Tumors
Cells
antigens
Antigens
neoplasms
T-lymphocytes
cell lines
T-Lymphocytes
Cell Line
cells
immunotherapy
Neoplasms
Therapeutics
Testicular Neoplasms
testes
Epitopes
therapeutics
Adoptive Immunotherapy

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

NYESO-1/LAGE-1s and prame are targets for antigen specific t cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine. / Pollack, Seth M.; Li, Yonqing; Blaisdell, Megan J.; Farrar, Erik A.; Chou, Jeffrey; Hoch, Benjamin L.; Loggers, Elizabeth T.; Rodler, Eve; Eary, Janet F.; Conrad, Ernest U.; Jones, Robin L.; Yee, Cassian.

In: PLoS One, Vol. 7, No. 2, e32165, 27.02.2012.

Research output: Contribution to journalArticle

Pollack, SM, Li, Y, Blaisdell, MJ, Farrar, EA, Chou, J, Hoch, BL, Loggers, ET, Rodler, E, Eary, JF, Conrad, EU, Jones, RL & Yee, C 2012, 'NYESO-1/LAGE-1s and prame are targets for antigen specific t cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine', PLoS One, vol. 7, no. 2, e32165. https://doi.org/10.1371/journal.pone.0032165
Pollack, Seth M. ; Li, Yonqing ; Blaisdell, Megan J. ; Farrar, Erik A. ; Chou, Jeffrey ; Hoch, Benjamin L. ; Loggers, Elizabeth T. ; Rodler, Eve ; Eary, Janet F. ; Conrad, Ernest U. ; Jones, Robin L. ; Yee, Cassian. / NYESO-1/LAGE-1s and prame are targets for antigen specific t cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine. In: PLoS One. 2012 ; Vol. 7, No. 2.
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title = "NYESO-1/LAGE-1s and prame are targets for antigen specific t cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine",
abstract = "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.",
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T1 - NYESO-1/LAGE-1s and prame are targets for antigen specific t cells in chondrosarcoma following treatment with 5-Aza-2-deoxycitabine

AU - Pollack, Seth M.

AU - Li, Yonqing

AU - Blaisdell, Megan J.

AU - Farrar, Erik A.

AU - Chou, Jeffrey

AU - Hoch, Benjamin L.

AU - Loggers, Elizabeth T.

AU - Rodler, Eve

AU - Eary, Janet F.

AU - Conrad, Ernest U.

AU - Jones, Robin L.

AU - Yee, Cassian

PY - 2012/2/27

Y1 - 2012/2/27

N2 - 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.

AB - 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.

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