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Active immunotherapy for advanced
intracranial murine tumors by using dendritic cell-tumor cell fusion
vaccines
Kjaergaard J, Wang LX, Kuriyama H, Shu S, Plautz
GE
Center for Surgery Research, Cleveland Clinic Foundation,
Cleveland, Ohio 44195, USA.
Object. Immunotherapy for malignant brain tumors by
active immunization or adoptive transfer of tumor antigen-specific T
lymphocytes has the potential to make up for some of the limitations
of current clinical therapy.
In this study, the authors tested whether active immunotherapy is
curative in mice bearing advanced, rapidly progressive intracranial
tumors.
Methods. Tumor vaccines
were created through electrofusion of dendritic cells (DCs) and
irradiated tumor cells to form multinucleated heterokaryons that
retained the potent antigen processing and costimulatory function of
DCs as well as the entire complement of tumor antigens.
Murine hosts bearing intracranial GL261 glioma or MCA 205 fibrosarcoma
were treated with a combination of local cranial radiotherapy,
intrasplenic vaccination with DC/tumor fusion cells, and anti-OX40R
(CD134) monoclonal antibody (mAb) 7 days after tumor
inoculation.
Whereas control mice had a median survival of approximately 20 days,
the treated mice underwent complete tumor regression that was
immunologically specific.
Seven days after vaccination treated mice demonstrated robust
infiltration of CD4+ and CD8+ T cells, which was exclusively confined
to the tumor without apparent neurological toxicity.
Cured mice survived longer than 120 days with no evidence of tumor
recurrence and resisted intracranial tumor challenge.
Conclusions. These data
indicate a strategy to achieve an antitumor response against tumors in
the central nervous system that is highly focused from both
immunological and anatomical perspectives.
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