Marked enhancement of antitumor immune responses in mouse brain tumor models by genetically modified dendritic cells producing Semliki Forest virus-mediated interleukin-12.

Abstract

OBJECT:

The authors evaluated dendritic cell (DC)-based immunotherapy for malignant brain tumor to improve its therapeutic efficacy.

METHODS:

Dendritic cells were isolated from bone marrow and pulsed with phosphate-buffered saline, Semliki Forest virus (SFV)-LacZ, retrovirus vector GCsap-interleukin (IL)-12, and SFV-IL-12, respectively, to treat mice bearing brain tumors of the B16 cell line. The results indicated that therapeutic immunization with DCs pulsed with SFV-IL-12 prolonged the survival of mice with established tumors. Semliki Forest virus induced apoptosis in DCs, which in turn facilitated the uptake of apoptotic cells by other DCs, thus providing a potential mechanism for enhanced immunogenicity.

CONCLUSIONS:

Therapy with DCs that have been pulsed with SFV-mediated IL-12 may be an excellent step in the development of new cancer vaccines. Intratumorally injected DCs that have been transiently transduced with IL-12 do not require pulsing of a source of tumor antigens to induce tumor regression.

• Authors: Ryuya Yamanaka, Susan A Zullo, Jay Ramsey, Naoki Yajima, Naoto Tsuchiya, Ryuichi Tanaka, Michael Blaese, Kleanthis G Xanthopoulos
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 97 Issue 3 Pg. 611-8 (Sep 2002) ISSN: 0022-3085 [Print] United States
• PMID: 12296646 (Publication Type: Journal Article)

Chemical References

• Interleukin-12
• Interferon-gamma

Topics

• Animals
• Apoptosis (immunology)
• Bone Marrow Cells
• Brain Neoplasms (immunology, therapy)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Dendritic Cells (immunology, virology)
• Genetic Therapy
• Genetic Vectors
• Glioma (immunology, therapy)
• Immunotherapy, Active
• Interferon-gamma (biosynthesis)
• Interleukin-12 (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Semliki forest virus (genetics)
• Transduction, Genetic
• Tumor Cells, Cultured (transplantation)