Screening of cytokines to enhance vaccine effects of heat shock protein 70-rich tumor cell lysate

Akira Ito, Masatake Fujioka, Kouji Tanaka, Takeshi Kobayashi, Hiroyuki Honda

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Heat shock proteins (HSPs) have been recognized as significant participants in immune reactions. We have previously reported that heat-treated cells expressing HSP70 can mediate potent antitumor immune responses. As successful immunotherapy is dependent on the host immune system, the present study evaluated whether systemic administration of immunocyte stimulatory and growth promoting cytokines could enhance heat-treated cell lysate vaccine (HCLV) immunization to further promote the antitumor immunity. After heating mouse melanoma B16 cells (43°C, 30 min) to elicit increased HSP70 expression, cells were lysed by freeze thawing to prepare HCLV. In approaches using a poorly immunogenic melanoma B16, the effects of various cytokines (IL-1β, -2, -4, -6 and -12, IFN-β and -γ, GM-CSF and TNF-α) were assessed in combination with HCLV. Syngenic C57BL/6 mice were immunized subcutaneously with HCLV twice, on days -14 and -7, while cytokines were injected intraperitoneally on day -7. Subcutaneous B16 cell challenge was performed on day 0. IL-12 significantly enhanced the efficacy of HCLV, compared to non-heated cell lysate vaccine (CLV) and non-vaccination. Systemic administration of recombinant IL-12 augmented the efficacy of HCLV, inducing protective immunity against tumor challenge and enhancing cytotoxicity assessed in primed splenocytes against B16 cells in treated mice. These results suggest that IL-12 represents an important modulator of antitumor immune responses induced by HCLV, and may facilitate further efforts to develop novel cancer immunotherapies based on HSP70-mediated vaccination.

Original languageEnglish
Pages (from-to)36-42
Number of pages7
JournalJournal of Bioscience and Bioengineering
Volume100
Issue number1
DOIs
Publication statusPublished - Jan 1 2005
Externally publishedYes

Fingerprint

HSP70 Heat-Shock Proteins
Vaccines
Tumors
Screening
Cells
Cytokines
Proteins
Hot Temperature
Neoplasms
Interleukin-12
Experimental Melanomas
Antigen-antibody reactions
Immunization
Thawing
Immunotherapy
Immune system
Granulocyte-Macrophage Colony-Stimulating Factor
Cytotoxicity
Immunity
Heat-Shock Proteins

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Screening of cytokines to enhance vaccine effects of heat shock protein 70-rich tumor cell lysate. / Ito, Akira; Fujioka, Masatake; Tanaka, Kouji; Kobayashi, Takeshi; Honda, Hiroyuki.

In: Journal of Bioscience and Bioengineering, Vol. 100, No. 1, 01.01.2005, p. 36-42.

Research output: Contribution to journalArticle

Ito, Akira ; Fujioka, Masatake ; Tanaka, Kouji ; Kobayashi, Takeshi ; Honda, Hiroyuki. / Screening of cytokines to enhance vaccine effects of heat shock protein 70-rich tumor cell lysate. In: Journal of Bioscience and Bioengineering. 2005 ; Vol. 100, No. 1. pp. 36-42.
@article{0ad15eb1430a4842a88a95e0353d35c0,
title = "Screening of cytokines to enhance vaccine effects of heat shock protein 70-rich tumor cell lysate",
abstract = "Heat shock proteins (HSPs) have been recognized as significant participants in immune reactions. We have previously reported that heat-treated cells expressing HSP70 can mediate potent antitumor immune responses. As successful immunotherapy is dependent on the host immune system, the present study evaluated whether systemic administration of immunocyte stimulatory and growth promoting cytokines could enhance heat-treated cell lysate vaccine (HCLV) immunization to further promote the antitumor immunity. After heating mouse melanoma B16 cells (43°C, 30 min) to elicit increased HSP70 expression, cells were lysed by freeze thawing to prepare HCLV. In approaches using a poorly immunogenic melanoma B16, the effects of various cytokines (IL-1β, -2, -4, -6 and -12, IFN-β and -γ, GM-CSF and TNF-α) were assessed in combination with HCLV. Syngenic C57BL/6 mice were immunized subcutaneously with HCLV twice, on days -14 and -7, while cytokines were injected intraperitoneally on day -7. Subcutaneous B16 cell challenge was performed on day 0. IL-12 significantly enhanced the efficacy of HCLV, compared to non-heated cell lysate vaccine (CLV) and non-vaccination. Systemic administration of recombinant IL-12 augmented the efficacy of HCLV, inducing protective immunity against tumor challenge and enhancing cytotoxicity assessed in primed splenocytes against B16 cells in treated mice. These results suggest that IL-12 represents an important modulator of antitumor immune responses induced by HCLV, and may facilitate further efforts to develop novel cancer immunotherapies based on HSP70-mediated vaccination.",
author = "Akira Ito and Masatake Fujioka and Kouji Tanaka and Takeshi Kobayashi and Hiroyuki Honda",
year = "2005",
month = "1",
day = "1",
doi = "10.1263/jbb.100.36",
language = "English",
volume = "100",
pages = "36--42",
journal = "Journal of Bioscience and Bioengineering",
issn = "1389-1723",
publisher = "The Society for Biotechnology, Japan",
number = "1",

}

TY - JOUR

T1 - Screening of cytokines to enhance vaccine effects of heat shock protein 70-rich tumor cell lysate

AU - Ito, Akira

AU - Fujioka, Masatake

AU - Tanaka, Kouji

AU - Kobayashi, Takeshi

AU - Honda, Hiroyuki

PY - 2005/1/1

Y1 - 2005/1/1

N2 - Heat shock proteins (HSPs) have been recognized as significant participants in immune reactions. We have previously reported that heat-treated cells expressing HSP70 can mediate potent antitumor immune responses. As successful immunotherapy is dependent on the host immune system, the present study evaluated whether systemic administration of immunocyte stimulatory and growth promoting cytokines could enhance heat-treated cell lysate vaccine (HCLV) immunization to further promote the antitumor immunity. After heating mouse melanoma B16 cells (43°C, 30 min) to elicit increased HSP70 expression, cells were lysed by freeze thawing to prepare HCLV. In approaches using a poorly immunogenic melanoma B16, the effects of various cytokines (IL-1β, -2, -4, -6 and -12, IFN-β and -γ, GM-CSF and TNF-α) were assessed in combination with HCLV. Syngenic C57BL/6 mice were immunized subcutaneously with HCLV twice, on days -14 and -7, while cytokines were injected intraperitoneally on day -7. Subcutaneous B16 cell challenge was performed on day 0. IL-12 significantly enhanced the efficacy of HCLV, compared to non-heated cell lysate vaccine (CLV) and non-vaccination. Systemic administration of recombinant IL-12 augmented the efficacy of HCLV, inducing protective immunity against tumor challenge and enhancing cytotoxicity assessed in primed splenocytes against B16 cells in treated mice. These results suggest that IL-12 represents an important modulator of antitumor immune responses induced by HCLV, and may facilitate further efforts to develop novel cancer immunotherapies based on HSP70-mediated vaccination.

AB - Heat shock proteins (HSPs) have been recognized as significant participants in immune reactions. We have previously reported that heat-treated cells expressing HSP70 can mediate potent antitumor immune responses. As successful immunotherapy is dependent on the host immune system, the present study evaluated whether systemic administration of immunocyte stimulatory and growth promoting cytokines could enhance heat-treated cell lysate vaccine (HCLV) immunization to further promote the antitumor immunity. After heating mouse melanoma B16 cells (43°C, 30 min) to elicit increased HSP70 expression, cells were lysed by freeze thawing to prepare HCLV. In approaches using a poorly immunogenic melanoma B16, the effects of various cytokines (IL-1β, -2, -4, -6 and -12, IFN-β and -γ, GM-CSF and TNF-α) were assessed in combination with HCLV. Syngenic C57BL/6 mice were immunized subcutaneously with HCLV twice, on days -14 and -7, while cytokines were injected intraperitoneally on day -7. Subcutaneous B16 cell challenge was performed on day 0. IL-12 significantly enhanced the efficacy of HCLV, compared to non-heated cell lysate vaccine (CLV) and non-vaccination. Systemic administration of recombinant IL-12 augmented the efficacy of HCLV, inducing protective immunity against tumor challenge and enhancing cytotoxicity assessed in primed splenocytes against B16 cells in treated mice. These results suggest that IL-12 represents an important modulator of antitumor immune responses induced by HCLV, and may facilitate further efforts to develop novel cancer immunotherapies based on HSP70-mediated vaccination.

UR - http://www.scopus.com/inward/record.url?scp=27644582468&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644582468&partnerID=8YFLogxK

U2 - 10.1263/jbb.100.36

DO - 10.1263/jbb.100.36

M3 - Article

C2 - 16233848

AN - SCOPUS:27644582468

VL - 100

SP - 36

EP - 42

JO - Journal of Bioscience and Bioengineering

JF - Journal of Bioscience and Bioengineering

SN - 1389-1723

IS - 1

ER -