Chaperone-rich cell lysates, immune activation and tumor vaccination

Yi - Zeng, Michael W. Graner, Emmanuel Katsanis

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

We have utilized a free-solution-isoelectric focusing technique (FS-IEF) to obtain chaperone-rich cell lysates (CRCL) fractions from clarified tumor homogenates. The FS-IEF technique for enriching multiple chaperones from tumor lysate is relatively easy and rapid, yielding sufficient immunogenic material for clinical use. We have shown that tumor-derived CRCL carry antigenic peptides. Dendritic cells (DCs) uptake CRCL and cross-present the chaperoned peptides to T cells. Tumor-derived CRCL induce protective immune responses against a diverse range of murine tumor types in different genetic backgrounds. When compared to purified heat shock protein 70 (HSP70), single antigenic peptide or unfractionated lysate, CRCL have superior ability to activate/mature DCs and are able to induce potent, long lasting and tumor specific T-cell-mediated immunity. While CRCL vaccines were effective as stand-alone therapies, the enhanced immunogenicity arising from CRCL-pulsed DC as a vaccine indicates that CRCL could be the antigen source of choice for DC-based anti-cancer immunotherapies. The nature of CRCL's enhanced immunogenicity may lie in the broader antigenic peptide repertoire as well as the superior immune activation capacity of CRCL. Exongenous CRCL also supply danger signals in the context of apoptotic tumor cells and enhance the immunogenicity of apoptotic tumor cells, leading to tumor-specific T cell dependent long-term immunity. Moreover, CRCL based vaccines can be effectively combined with chemotherapy to treat cancer. Our findings indicate that CRCL have prominent adjuvant effects and are effective sources of tumor antigens for pulsing DCs. Tumor-derived CRCL are promising anti-cancer vaccines that warrant clinical research and development.

Original languageEnglish (US)
Pages (from-to)329-338
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume55
Issue number3
DOIs
StatePublished - Mar 2006

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Vaccination
Neoplasms
Dendritic Cells
Vaccines
Isoelectric Focusing
T-Lymphocytes
Peptides
Peptide T
Cancer Vaccines
HSP70 Heat-Shock Proteins
Neoplasm Antigens
Cellular Immunity
Immunotherapy
Immunity
Antigens
Drug Therapy

Keywords

  • Chaperone/Heat shock proteins
  • Dendritic cells
  • Tumor
  • Vaccine

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Chaperone-rich cell lysates, immune activation and tumor vaccination. / Zeng, Yi -; Graner, Michael W.; Katsanis, Emmanuel.

In: Cancer Immunology, Immunotherapy, Vol. 55, No. 3, 03.2006, p. 329-338.

Research output: Contribution to journalArticle

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