Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro

G. Li, Y. Zeng, X. Chen, N. Larmonier, M. Sepassi, M. W. Graner, Samita Andreansky, M. A. Brewer, E. Katsanis

Research output: Contribution to journalArticle

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Abstract

Tumour-derived chaperone-rich cell lysate (CRCL), which is made up of numerous heat shock proteins, has been used successfully to generate tumour-specific T cell responses and protective immunity against a wide range of murine tumours. In this study, we have investigated the potency of human ovarian cancer-derived CRCL to activate dendritic cells (DC) and to generate tumour-specific T cells in vitro. CRCL was generated from primary ovarian cancers and SKOV3-A2, a HER2/neu, Wilm's tumour gene 1 (WT1) and human leucocyte antigen (HLA)-A2 positive human ovarian tumour cell line. Peripheral blood mononuclear cells from both HLA-A2+ healthy donors and HLA-A2 + ovarian cancer patients were stimulated weekly with autologous DC loaded with ovarian tumour-derived CRCL. After four to six stimulations in vitro, specific cytokine secretion and cytotoxicity were measured. CRCL promoted interleukin (IL)-12 secretion and enhanced the immunostimulatory capacity of DC. T cells from healthy controls and from ovarian cancer patients secreted higher amounts of interferon-γ following in vitro restimulation with ovarian cancer-derived CRCL than with HER2/neu or WT1 peptide-pulsed DC. We were also able to generate cytotoxic T lymphocyte activity against cancer-specific antigens such as HER2/neu and WT1 from all healthy donors, but from only one of the four ovarian cancer patients with bulky disease. These preliminary results substantiate further the concept that CRCL may prove to be a potent adjuvant for women suffering from ovarian cancer and that this personalized vaccine may be a promising approach for active immunotherapy.

Original languageEnglish
Pages (from-to)136-145
Number of pages10
JournalClinical and Experimental Immunology
Volume148
Issue number1
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Ovarian Neoplasms
T-Lymphocytes
varespladib methyl
Neoplasms
Dendritic Cells
HLA Antigens
Tissue Donors
Genes
In Vitro Techniques
Active Immunotherapy
Cancer Vaccines
Cytotoxic T-Lymphocytes
Interleukin-12
Heat-Shock Proteins
Tumor Cell Line
Interferons
Immunity
Blood Cells
Cytokines
Antigens

Keywords

  • Cancer vaccine
  • Chaperone-rich cell lysate (CRCL)
  • Dendritic cell (DC)
  • Heat shock protein (HSP)
  • Ovarian cancer

ASJC Scopus subject areas

  • Immunology

Cite this

Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro. / Li, G.; Zeng, Y.; Chen, X.; Larmonier, N.; Sepassi, M.; Graner, M. W.; Andreansky, Samita; Brewer, M. A.; Katsanis, E.

In: Clinical and Experimental Immunology, Vol. 148, No. 1, 01.04.2007, p. 136-145.

Research output: Contribution to journalArticle

Li, G, Zeng, Y, Chen, X, Larmonier, N, Sepassi, M, Graner, MW, Andreansky, S, Brewer, MA & Katsanis, E 2007, 'Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro', Clinical and Experimental Immunology, vol. 148, no. 1, pp. 136-145. https://doi.org/10.1111/j.1365-2249.2007.03323.x
Li, G. ; Zeng, Y. ; Chen, X. ; Larmonier, N. ; Sepassi, M. ; Graner, M. W. ; Andreansky, Samita ; Brewer, M. A. ; Katsanis, E. / Human ovarian tumour-derived chaperone-rich cell lysate (CRCL) elicits T cell responses in vitro. In: Clinical and Experimental Immunology. 2007 ; Vol. 148, No. 1. pp. 136-145.
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