CpG oligonucleotides enhance the tumor antigen-specific immune response of a granulocyte macrophage colony-stimulating factor-based vaccine strategy in neuroblastoma

Anthony D. Sandler, Hiroshi Chihara, Gen Kobayashi, Xiaoyan Zhu, Michal A. Miller, David Scott, Arthur M. Krieg

Research output: Contribution to journalArticle

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Abstract

Granulocyte macrophage colony-stimulating factor (GM-CSF)-transduced autologous tumor cells form the basis of many immunotherapeutic strategies. We tested whether combining this approach with T-helper 1 (Th-1)-like immunostimulatory CpG oligodeoxynucleotides (CpG ODNs) would improve therapeutic efficacy in an established model of murine neuroblastoma. The weakly immunogenic Neuro-2a cell line was used in syngeneic A/J mice. CpG 1826 was tested for its antitumor effect alone and as an adjuvant to Neuro-2a cells retrovirally transduced to express murine GM-CSF (GM/Neuro-2a). Three days after wild-type (WT) tumor cell inoculation, mice in different groups were s.c. vaccinated in the opposite leg with combinations of WT neuro2a, irradiated (15 Gy) WT or GM/Neuro-2a transfectants with or without CpG 1826 (200 μg). To test for the induction of memory responses, mice that rejected their tumor were rechallenged with WT Neuro-2a (1 × 106) 7 weeks after vaccination. All of the mice in the control (unvaccinated) group died within 3 weeks after Neuro-2a inoculation. Most of the vaccinated groups had only minimal- to-modest antitumor responses, and the mice succumbed to tumor. Tumor growth was remarkably inhibited in the group of mice that received irradiated GM/Neuro-2a plus CpG and four (50%) of eight mice in this group survived tumor free. Tumor-free mice were resistant to further WT tumor cell challenge, indicating a memory response. Mechanistic studies showed that CpG alone induced a favorable Th-1-like cytokine immune response and vaccine-induced tumor cell killing was dependent on both CD4 and CD8 T cells that killed tumor cell targets by apoptosis. These results demonstrate that CpG ODNs enhanced the antitumor effect of irradiated GM-CSF secreting Neuro-2a cells. This vaccine strategy elicits a potent tumor antigen-specific immune response against established murine neuroblastoma and generates systemic neuroblastoma-specific immunity.

Original languageEnglish (US)
Pages (from-to)394-399
Number of pages6
JournalCancer Research
Volume63
Issue number2
StatePublished - Jan 15 2003
Externally publishedYes

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Neoplasm Antigens
Granulocyte-Macrophage Colony-Stimulating Factor
Neuroblastoma
Oligonucleotides
Vaccines
Neoplasms
Oligodeoxyribonucleotides
Cancer Vaccines
Immunity
Leg
Vaccination
Apoptosis
Cytokines
T-Lymphocytes
Cell Line
Control Groups
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

CpG oligonucleotides enhance the tumor antigen-specific immune response of a granulocyte macrophage colony-stimulating factor-based vaccine strategy in neuroblastoma. / Sandler, Anthony D.; Chihara, Hiroshi; Kobayashi, Gen; Zhu, Xiaoyan; Miller, Michal A.; Scott, David; Krieg, Arthur M.

In: Cancer Research, Vol. 63, No. 2, 15.01.2003, p. 394-399.

Research output: Contribution to journalArticle

Sandler, Anthony D. ; Chihara, Hiroshi ; Kobayashi, Gen ; Zhu, Xiaoyan ; Miller, Michal A. ; Scott, David ; Krieg, Arthur M. / CpG oligonucleotides enhance the tumor antigen-specific immune response of a granulocyte macrophage colony-stimulating factor-based vaccine strategy in neuroblastoma. In: Cancer Research. 2003 ; Vol. 63, No. 2. pp. 394-399.
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