Focal adhesion kinase as an immunotherapeutic target.

Abstract

BACKGROUND:

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, FAK(143-157) 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.

• Authors: Hiroya Kobayashi, Makoto Azumi, Yuka Kimura, Keisuke Sato, Naoko Aoki, Shoji Kimura, Masaru Honma, Hajime Iizuka, Masatoshi Tateno, Esteban Celis
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 58 Issue 6 Pg. 931-40 (Jun 2009) ISSN: 1432-0851 [Electronic] Germany
• PMID: 18941742 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• Peptide Fragments
• Focal Adhesion Protein-Tyrosine Kinases

Topics

• Antigens, Neoplasm (immunology)
• Blotting, Western
• CD4-Positive T-Lymphocytes (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Focal Adhesion Protein-Tyrosine Kinases (immunology)
• Genes, MHC Class II (physiology)
• Humans
• Immunoenzyme Techniques
• Immunotherapy
• Melanoma (therapy)
• Peptide Fragments (immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Tumor Cells, Cultured