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Dendritic cells pulsed with glioma lysates induce immunity against
syngeneic intracranial gliomas and increase survival of tumor-bearing
mice Pellegatta, S.1; Poliani,
P.L.2; Corno, D.1; Grisoli,
M.3; Cusimano, M.1; Ubiali,
F.4; Baggi, F.4; Bruzzone,
M.G.3; Finocchiaro, G.1
Affiliations: 1: Department
of Experimental Neuro-Oncology, Istituto Nazionale Neurologico Besta,
Milano, Italy 2: Department of Pathology,
University of Brescia, Brescia, Italy 3: Department of Radiology, Istituto
Nazionale Neurologico Besta, Milano, Italy 4: Department of Neuromuscular
Disorders, Istituto Nazionale Neurologico Besta, Milano, Italy
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In recent years, the use of dendritic cells (DC), the most powerful
antigen presenting cells, has been proposed for the creation of
vaccines against gliomas.
This approach has been demonstrated to be
safe and non-toxic in phase I or I-II trials (2, 3).
Immunotherapy
plays a central role in the search for new treatments for glioblastoma
multiforme (GBM).
In particular, several phase I studies have been
performed using DC pulsed by GBM proteins as a vaccine for patients
with relapsing GBM.
The studies demonstrated that DC vaccination is
safe and may produce a significant increase in overall survival.
As
the first step in the preparation of appropriate conditions for a
clinical evaluation in Italy, we have performed pre-clinical
experiments on immune-competent mice injected intra-cerebrally with
syngeneic GL261GBM cells and treated subcutaneously and intra-tumorally
with DC loaded with a GL261 homogenate.
These results show that
vaccination with DC pulsed with a tumor lysate increases considerably
survival in mice bearing intracranial glioblastomas and supports the
development of DC-based clinical trials for patients with
glioblastomas that do not respond to standard therapies.Keywords:
Glioma; Dendritic Cells; Immunotherapy
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