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 journalArticle

3 Citations (Scopus)

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 1 2009
Externally publishedYes

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
Neoplasm Antigens
Neoplasms
Melanoma
Peptides
Helper-Inducer T-Lymphocytes
T-Lymphocytes
Immunotherapy
Focal Adhesion Kinase 1
T-Lymphoid Precursor Cells
T-Lymphocyte Epitopes
Cellular Immunity
Protein-Tyrosine Kinases
Dendritic Cells
Prostate
Epitopes
Ovary
Colon
Vaccination
Breast

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

Kobayashi, H., Azumi, M., Kimura, Y., Sato, K., Aoki, N., Kimura, S., ... Celis, E. (2009). Focal adhesion kinase as an immunotherapeutic target. Cancer Immunology, Immunotherapy, 58(6), 931-940. https://doi.org/10.1007/s00262-008-0608-0

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 journalArticle

Kobayashi, H, Azumi, M, Kimura, Y, Sato, K, Aoki, N, Kimura, S, Honma, M, Iizuka, H, Tateno, M & Celis, E 2009, 'Focal adhesion kinase as an immunotherapeutic target', Cancer Immunology, Immunotherapy, vol. 58, no. 6, pp. 931-940. https://doi.org/10.1007/s00262-008-0608-0
Kobayashi H, Azumi M, Kimura Y, Sato K, Aoki N, Kimura S et al. Focal adhesion kinase as an immunotherapeutic target. Cancer Immunology, Immunotherapy. 2009 Jun 1;58(6):931-940. https://doi.org/10.1007/s00262-008-0608-0
Kobayashi, Hiroya ; Azumi, Makoto ; Kimura, Yuka ; Sato, Keisuke ; Aoki, Naoko ; Kimura, Shoji ; Honma, Masaru ; Iizuka, Hajime ; Tateno, Masatoshi ; Celis, Esteban. / Focal adhesion kinase as an immunotherapeutic target. In: Cancer Immunology, Immunotherapy. 2009 ; Vol. 58, No. 6. pp. 931-940.
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