TY - JOUR
T1 - Antiglioma immunological memory in response to conditional cytotoxic/immune-stimulatory gene therapy
T2 - Humoral and cellular immunity lead to tumor regression
AU - Muhammad, A. K.M.Ghulam
AU - Candolfi, Marianela
AU - King, Gwendalyn D.
AU - Yagiz, Kader
AU - Foulad, David
AU - Mineharu, Yohei
AU - Kroeger, Kurt M.
AU - Treuer, Katherine A.
AU - Nichols, W. Stephen
AU - Sanderson, Nicholas S.
AU - Yang, Jieping
AU - Khayznikov, Maksim
AU - Van Rooijen, Nico
AU - Lowenstein, Pedro R.
AU - Castro, Maria G.
PY - 2009/10/1
Y1 - 2009/10/1
N2 - Purpose: Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme. Experimental Design: Wedeveloped a combined treatment using an adenovirus (Ad) expressing fms-like tyrosine kinase-3 ligand (Flt3L),which induces the infiltration of immune cells into the tumor microenvironment, and an Ad expressing herpes simplex virus-1-thymidine kinase (TK), which kills proliferating tumor cells in the presence of ganciclovir. Results: This treatment induced immunologicalmemory that led to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastomamultiforme implanted intradermally. Rechallenged long-termsurvivors exhibited anti-glioblastoma multiforme-specific T cells and displayed specific delayedtype hypersensitivity. Using depleting antibodies,we showed that rejection of the second tumor was dependent on CD8+ T cells. Circulating anti
AB - Purpose: Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme. Experimental Design: Wedeveloped a combined treatment using an adenovirus (Ad) expressing fms-like tyrosine kinase-3 ligand (Flt3L),which induces the infiltration of immune cells into the tumor microenvironment, and an Ad expressing herpes simplex virus-1-thymidine kinase (TK), which kills proliferating tumor cells in the presence of ganciclovir. Results: This treatment induced immunologicalmemory that led to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastomamultiforme implanted intradermally. Rechallenged long-termsurvivors exhibited anti-glioblastoma multiforme-specific T cells and displayed specific delayedtype hypersensitivity. Using depleting antibodies,we showed that rejection of the second tumor was dependent on CD8+ T cells. Circulating anti
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U2 - 10.1158/1078-0432.CCR-09-1087
DO - 10.1158/1078-0432.CCR-09-1087
M3 - Article
C2 - 19789315
AN - SCOPUS:70349941137
VL - 15
SP - 6113
EP - 6127
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 19
ER -