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Identification of SPARC as a candidate target antigen for immunotherapy of various cancers

Mitsuhiro Inoue1, Satoru Senju, Shinya Hirata

  • 1Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

International Journal of Cancer
|January 12, 2010
PubMed

Insights

Secreted protein acidic and rich in cysteine (SPARC) is overexpressed in several cancers. SPARC-derived peptides successfully induced human cytotoxic T lymphocytes (CTLs) that target and inhibit cancer cells, suggesting SPARC as a promising immunotherapy target.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Identifying tumor-associated antigens (TAAs) is crucial for effective cancer immunotherapy.
  • Secreted protein acidic and rich in cysteine (SPARC) is overexpressed in gastric, pancreatic, and colorectal cancers.
  • SPARC's overexpression in cancer tissues, not normal ones, makes it a potential TAA.

Purpose of the Study:

  • To identify HLA-A24 (A*2402)-restricted and SPARC-derived cytotoxic T lymphocyte (CTL) epitopes.
  • To induce and characterize SPARC-reactive human CTLs for cancer immunotherapy.
  • To evaluate the in vivo efficacy of SPARC-specific CTLs against human tumors.

Main Methods:

  • Genome-wide cDNA microarray analysis to identify SPARC overexpression.
  • In vitro induction of human CTLs using SPARC-derived peptides (SPARC-A24-1 and SPARC-A24-4) in HLA-A24 (A*2402) positive individuals.
  • Assessment of CTL cytotoxicity against cancer cells expressing SPARC and HLA-A24 (A*2402).
  • In vivo tumor inhibition studies using adoptive transfer of SPARC-specific CTLs in immunodeficient mice.

Main Results:

  • SPARC gene was found to be overexpressed in gastric, pancreatic, and colorectal cancer tissues.
  • SPARC-A24-1 and SPARC-A24-4 peptides successfully induced SPARC-reactive human CTLs.
  • Induced CTLs demonstrated specific cytotoxicity against cancer cells expressing SPARC and HLA-A24 (A*2402).
  • Adoptive transfer of SPARC-specific CTLs inhibited tumor growth in vivo.

Conclusions:

  • SPARC is a viable tumor-associated antigen for cancer immunotherapy.
  • SPARC-derived peptides can be used to generate effective anti-cancer immune responses.
  • SPARC-specific CTLs hold potential for treating SPARC-expressing and HLA-A24 (A*2402)-positive cancers.

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