Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity

Yi - Zeng, Hanping Feng, Michael W. Graner, Emmanuel Katsanis

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

We have utilized a free-solution isoelectric focusing technique (FS-IEF) to obtain chaperone-rich cell lysate (CRCL) fractions from clarified tumor homogenates and have previously reported on their vaccinating potential. To better understand the underlying mechanisms as well as to improve on the immunizing efficacy of tumor-derived chaperone complexes, in the present study we examined the effects of CRCL-loaded dendritic cells (DCs) against 12B1, an aggressive bcr-abl+ murine leukemia tumor. We found that DCs incubated with 12B1-derived CRCL had higher expression of CD40 and major histocompatibility complex class II (MHC-II) on their cell surface, produced more interleukin-12 (IL-12), and had superior immunostimulatory capacity in a mixed leukocyte reaction (MLR) when compared with DCs exposed to unfractionated tumor lysate or purified heat-shock protein 70 (HSP70). Vaccination of mice with 12B1 CRCL-pulsed DCs significantly prolonged their survival, with more than 80% of mice rejecting their tumors following a lethal challenge with live 12B1 compared with those immunized with tumor lysate or HSP70-loaded DCs. The protective immunity generated was tumor specific, long lasting, and both CD4+ and CD8+ T-cell dependent. Moreover, immunization with CRCL-loaded DCs resulted in a 75% cure rate in mice with pre-existing 12B1 tumors. Our findings indicate that CRCL has prominent adjuvant effects and is a very effective source of tumor antigen for pulsing DCs. FS-IEF-derived CRCL-pulsed DCs are a promising anticancer vaccine that warrants clinical research and development.

Original languageEnglish (US)
Pages (from-to)4485-4491
Number of pages7
JournalBlood
Volume101
Issue number11
DOIs
StatePublished - Jun 1 2003

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Dendritic Cells
Tumors
Immunity
Neoplasms
HSP70 Heat-Shock Proteins
Isoelectric Focusing
Immunization
Mixed Lymphocyte Culture Test
T-cells
Neoplasm Antigens
Interleukin-12
Major Histocompatibility Complex
Leukemia
Vaccination
Vaccines
T-Lymphocytes
Research

ASJC Scopus subject areas

  • Hematology

Cite this

Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity. / Zeng, Yi -; Feng, Hanping; Graner, Michael W.; Katsanis, Emmanuel.

In: Blood, Vol. 101, No. 11, 01.06.2003, p. 4485-4491.

Research output: Contribution to journalArticle

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abstract = "We have utilized a free-solution isoelectric focusing technique (FS-IEF) to obtain chaperone-rich cell lysate (CRCL) fractions from clarified tumor homogenates and have previously reported on their vaccinating potential. To better understand the underlying mechanisms as well as to improve on the immunizing efficacy of tumor-derived chaperone complexes, in the present study we examined the effects of CRCL-loaded dendritic cells (DCs) against 12B1, an aggressive bcr-abl+ murine leukemia tumor. We found that DCs incubated with 12B1-derived CRCL had higher expression of CD40 and major histocompatibility complex class II (MHC-II) on their cell surface, produced more interleukin-12 (IL-12), and had superior immunostimulatory capacity in a mixed leukocyte reaction (MLR) when compared with DCs exposed to unfractionated tumor lysate or purified heat-shock protein 70 (HSP70). Vaccination of mice with 12B1 CRCL-pulsed DCs significantly prolonged their survival, with more than 80{\%} of mice rejecting their tumors following a lethal challenge with live 12B1 compared with those immunized with tumor lysate or HSP70-loaded DCs. The protective immunity generated was tumor specific, long lasting, and both CD4+ and CD8+ T-cell dependent. Moreover, immunization with CRCL-loaded DCs resulted in a 75{\%} cure rate in mice with pre-existing 12B1 tumors. Our findings indicate that CRCL has prominent adjuvant effects and is a very effective source of tumor antigen for pulsing DCs. FS-IEF-derived CRCL-pulsed DCs are a promising anticancer vaccine that warrants clinical research and development.",
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