Antiglioma immunological memory in response to conditional cytotoxic/immune-stimulatory gene therapy: Humoral and cellular immunity lead to tumor regression

A. K.M.Ghulam Muhammad, Marianela Candolfi, Gwendalyn D. King, Kader Yagiz, David Foulad, Yohei Mineharu, Kurt M. Kroeger, Katherine A. Treuer, W. Stephen Nichols, Nicholas S. Sanderson, Jieping Yang, Maksim Khayznikov, Nico Van Rooijen, Pedro R. Lowenstein, Maria G. Castro

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)6113-6127
Number of pages15
JournalClinical Cancer Research
Volume15
Issue number19
DOIs
StatePublished - Oct 1 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Antiglioma immunological memory in response to conditional cytotoxic/immune-stimulatory gene therapy: Humoral and cellular immunity lead to tumor regression'. Together they form a unique fingerprint.

Cite this