Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation

Masaru Udagawa, Chie Kudo-Saito, Go Hasegawa, Kazuhito Yano, Aiko Yamamoto, Masae Yaguchi, Masahiro Toda, Ichiro Azuma, Takehisa Iwai, Yutaka Kawakami

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Abstract

Purpose: We developed an effective immunotherapy, which could induce antitumor immune responses against shared and unique tumor antigens expressed in autologous tumors. Experimental Design: Intratumoral administration of dendritic cells is one of the individualized immunotherapies; however, the antitumor activity is relatively weak. In this study, we attempted to enhance the antitumor efficacy of the i.t. dendritic cell administration by combining dendritic cells stimulated with Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS) additionally with cryoablative pretreatment of tumors and analyzed the therapeutic mechanisms. Results: These two modifications (cryoablation of tumors and BCG-CWS stimulation of dendritic cells) significantly increases the antitumor effect on both the treated tumor and the untreated tumor, which was distant at the opposite side, in a bilateral s.c. murine CT26 colon cancer model. Further analysis of the augmented antitumor effects revealed that the cryoablative pretreatment enhances the uptake of tumor antigens by the introduced dendritic cells, resulting in the induction of tumor-specific CD8+ T cells responsible for the in vivo tumor regression of both treated and remote untreated tumors. This novel combination i.t. dendritic cell immunotherapy was effective against well-established large tumors. The antitumor efficacy was further enhanced by depletion of CD4+CD25 +FoxP3+ regulatory T cells. Conclusions: This novel dendritic cell immunotherapy with i.t. administration of BCG-CWS-treated dendritic cells following tumor cryoablation could be used for the therapy of cancer patients with multiple metastases.

Original languageEnglish
Pages (from-to)7465-7475
Number of pages11
JournalClinical Cancer Research
Volume12
Issue number24
DOIs
Publication statusPublished - 2006 Dec 15

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Cell Wall Skeleton
Mycobacterium bovis
Dendritic Cells
Neoplasms
Immunotherapy
Cryosurgery
Neoplasm Antigens
Regulatory T-Lymphocytes
Colonic Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation. / Udagawa, Masaru; Kudo-Saito, Chie; Hasegawa, Go; Yano, Kazuhito; Yamamoto, Aiko; Yaguchi, Masae; Toda, Masahiro; Azuma, Ichiro; Iwai, Takehisa; Kawakami, Yutaka.

In: Clinical Cancer Research, Vol. 12, No. 24, 15.12.2006, p. 7465-7475.

Research output: Contribution to journalArticle

Udagawa, Masaru ; Kudo-Saito, Chie ; Hasegawa, Go ; Yano, Kazuhito ; Yamamoto, Aiko ; Yaguchi, Masae ; Toda, Masahiro ; Azuma, Ichiro ; Iwai, Takehisa ; Kawakami, Yutaka. / Enhancement of immunologic tumor regression by intratumoral administration of dendritic cells in combination with cryoablative tumor pretreatment and Bacillus Calmette-Guerin cell wall skeleton stimulation. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 24. pp. 7465-7475.
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abstract = "Purpose: We developed an effective immunotherapy, which could induce antitumor immune responses against shared and unique tumor antigens expressed in autologous tumors. Experimental Design: Intratumoral administration of dendritic cells is one of the individualized immunotherapies; however, the antitumor activity is relatively weak. In this study, we attempted to enhance the antitumor efficacy of the i.t. dendritic cell administration by combining dendritic cells stimulated with Bacillus Calmette-Guerin cell wall skeleton (BCG-CWS) additionally with cryoablative pretreatment of tumors and analyzed the therapeutic mechanisms. Results: These two modifications (cryoablation of tumors and BCG-CWS stimulation of dendritic cells) significantly increases the antitumor effect on both the treated tumor and the untreated tumor, which was distant at the opposite side, in a bilateral s.c. murine CT26 colon cancer model. Further analysis of the augmented antitumor effects revealed that the cryoablative pretreatment enhances the uptake of tumor antigens by the introduced dendritic cells, resulting in the induction of tumor-specific CD8+ T cells responsible for the in vivo tumor regression of both treated and remote untreated tumors. This novel combination i.t. dendritic cell immunotherapy was effective against well-established large tumors. The antitumor efficacy was further enhanced by depletion of CD4+CD25 +FoxP3+ regulatory T cells. Conclusions: This novel dendritic cell immunotherapy with i.t. administration of BCG-CWS-treated dendritic cells following tumor cryoablation could be used for the therapy of cancer patients with multiple metastases.",
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AU - Hasegawa, Go

AU - Yano, Kazuhito

AU - Yamamoto, Aiko

AU - Yaguchi, Masae

AU - Toda, Masahiro

AU - Azuma, Ichiro

AU - Iwai, Takehisa

AU - Kawakami, Yutaka

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