Details

Autor(en) / Beteiligte

• OKADA, Hideho
• TSUGAWA, Takahiko
• CHAMBERS, William H
• POTTER, Douglas M
• STORKUS, Walter J
• POLLACK, Ian F
• SATO, Hidemitsu
• KUWASHIMA, Naruo
• GAMBOTTO, Andrea
• OKADA, Kaori
• DUSAK, Jill E
• FELLOWS-MAYLE, Wendy K
• PAPWORTH, Glenn D
• WATKINS, Simon C

Titel

Delivery of interferon-α transfected dendritic cells into central nervous system tumors enhances the antitumor efficacy of peripheral peptide-based vaccines

Ist Teil von

• Cancer research (Chicago, Ill.), 2004-08, Vol.64 (16), p.5830-5838

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2004

Quelle

MEDLINE

Beschreibungen/Notizen

• We evaluated the effects, on immunity and survival, of injection of interferon (IFN)-alpha-transfected dendritic cells (DC-IFN-alpha) into intracranial tumors in mice immunized previously with syngeneic dendritic cells (DCs) pulsed either with ovalbumin-derived CTL or T helper epitopes. These immunizations protected animals from s.c. challenge with ovalbumin-expressing M05 melanoma (class I+ and class II-negative). Notably, antiovalbumin CTL responses were observed in animals vaccinated with an ovalbumin-derived T helper epitope but only after the mice were challenged with M05 cells. This cross-priming of CTL was dependent on both CD4+ and CD8+ T cells. Because we observed that s.c., but not intracranial, tumors were infiltrated with CD11c+ DCs, and because IFN-alpha promotes the activation and survival of both DCs and T cells, we evaluated the combinational antitumor effects of injecting adenoviral (Ad)-IFN-alpha-engineered DCs into intracranial M05 tumors in preimmunized mice. Delivery of DC-IFN-alpha prolonged survival. This was most notable for animals prevaccinated with both the CTL and T helper ovalbumin epitopes, with 60% (6 of 10) of mice (versus 0 of 10 of control animals) surviving for > 80 days after tumor challenge. DC-IFN-alpha appeared to persist longer than mock-transfected DCs within the intracranial tumor microenvironment, and DC-IFN-alpha-treated mice exhibited enhanced levels of ovalbumin-specific CTL in draining cervical lymph nodes. On the basis of these results, we believe that local expression of IFN-alpha by DCs within the intracranial tumor site may enhance the clinical efficacy of peripheral vaccine approaches for brain tumors.