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

研究成果: Contribution to journalArticle査読

23 被引用数 (Scopus)


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.

ジャーナルJournal of Bioscience and Bioengineering
出版ステータス出版済み - 2005

All Science Journal Classification (ASJC) codes

  • バイオテクノロジー
  • バイオエンジニアリング
  • 応用微生物学とバイオテクノロジー


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