Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 931-940 |
| Number of pages | 10 |
| Journal | Cancer Immunology, Immunotherapy |
| Volume | 58 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 1 2009 |
| Externally published | Yes |
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Keywords
- CD4 helper T lymphocytes
- Focal adhesion kinase
- Immunotherapy
- Major histocompatibility complex class II
- Peptide epitope
- Tumor antigens
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
- Cancer Research
Cite this
Focal adhesion kinase as an immunotherapeutic target. / Kobayashi, Hiroya; Azumi, Makoto; Kimura, Yuka; Sato, Keisuke; Aoki, Naoko; Kimura, Shoji; Honma, Masaru; Iizuka, Hajime; Tateno, Masatoshi; Celis, Esteban.
In: Cancer Immunology, Immunotherapy, Vol. 58, No. 6, 01.06.2009, p. 931-940.Research output: Contribution to journal › Article
}
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
PY - 2009/6/1
Y1 - 2009/6/1
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
UR - http://www.scopus.com/inward/record.url?scp=63949087985&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63949087985&partnerID=8YFLogxK
U2 - 10.1007/s00262-008-0608-0
DO - 10.1007/s00262-008-0608-0
M3 - Article
C2 - 18941742
AN - SCOPUS:63949087985
VL - 58
SP - 931
EP - 940
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 6
ER -