TY - JOUR
T1 - Focal adhesion kinase as an immunotherapeutic target
AU - Kobayashi, Hiroya
AU - Azumi, Makoto
AU - Kimura, Yuka
AU - Sato, Keisuke
AU - Aoki, Naoko
AU - Kimura, Shoji
AU - Honma, Masaru
AU - Iizuka, Hajime
AU - Tateno, Masatoshi
AU - Celis, Esteban
N1 - Funding Information:
Acknowledgments E. Celis received grant support from NIH grants P50CA91956, R01CA80782 and R01CA103921.
PY - 2009/6
Y1 - 2009/6
N2 - Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses. Methods: To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients. Results: Two synthetic peptides, FAK143-157 and FAK 1,000-1,014, induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients. Conclusions: Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors.
AB - Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses. Methods: To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients. Results: Two synthetic peptides, FAK143-157 and FAK 1,000-1,014, induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients. Conclusions: Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors.
KW - CD4 helper T lymphocytes
KW - Focal adhesion kinase
KW - Immunotherapy
KW - Major histocompatibility complex class II
KW - Peptide epitope
KW - Tumor antigens
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U2 - 10.1007/s00262-008-0608-0
DO - 10.1007/s00262-008-0608-0
M3 - Article
C2 - 18941742
AN - SCOPUS:63949087985
SN - 0340-7004
VL - 58
SP - 931
EP - 940
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
IS - 6
ER -