Focal adhesion kinase as an immunotherapeutic target

Hiroya Kobayashi, Makoto Azumi, Yuka Kimura, Keisuke Sato, Naoko Aoki, Shoji Kimura, Masaru Honma, Hajime Iizuka, Masatoshi Tateno, Esteban Celis

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 languageEnglish (US)
Pages (from-to)931-940
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume58
Issue number6
DOIs
StatePublished - Jun 2009
Externally publishedYes

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

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