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Overcoming brain immune privilege with Flt3L and TK treatment in a recurrent rat glioma model
Author(s) -
King Gwendalyn D.,
Muhammad Ghulam,
Larocque Daniel,
Candolfi Marianela,
Bergeron Josee,
Liu Chunyan,
Kroeger Kurt,
Van Rooijen Nico,
Lowenstein Pedro R.,
Castro Maria G.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1077.9
Subject(s) - immune system , cd8 , glioma , in vivo , immune privilege , cancer research , elispot , in vitro , immunology , brain tumor , antigen , biology , medicine , chemistry , pathology , biochemistry , microbiology and biotechnology
GBM is an invasive primary brain cancer which invariably recurs. Intratumoral treatment of a large syngeneic rat model of GBM with AdFlt3L and AdTK induce ~70% long term survival. Here we evaluated Flt3L and TK treatment in a model of recurrence. Long term GBM survivors post‐therapy were rechallenged with GBM in the contralateral striatum. 100% of animals survived to ~200 days post‐GBM rechallenge. In vitro elispot assays detected tumor specific circulating T cells; in vivo DTH was detected in all long term survivors. Depletion of CD8+ cells but not CD4+ or macrophages abrogated survival of GBM rechallenged animals. To model neo‐antigen expression as a means of tumor escape, we generated CNS‐1 cells stably expressing hemagglutinin CNS1‐HA cells grew similarly in vitro and in vivo and responded to Ad‐Flt3L/Ad‐TK treatment in an indistinguishable fashion from CNS1 tumors. When long term survivors were rechallenged with CNS‐1HA cells, INF γ secreting T‐cells were detected against HA. We conclude that Ad‐Flt3L/Ad‐TK treatment induces immunological memory that protects against recurrence and tumor escape by overcoming brain immune privilege. Funding: NIH/NINDS Grant 1R01 NS44556.01; 1R21‐NSO54143.01; 1UO1 NS052465.01; 1RO1 NS 054193.01; RO1 NS 42893.01, U54 NS045309‐01 and 1R21 NS047298‐01 to P.R.L. GDK and MC are supported by NIH/NINDS 1F32 N50503034‐01 and 1F32 NS058156.01 respectively.