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

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.