Improved antitumour immunity in murine neuroblastoma using a combination of IL-2 and IL-12

British Journal of Cancer
K E SiapatiS L Hart

Abstract

Neuroblastoma immunotherapy using cytokine-modified tumour cells has been tested in clinical trials. However, because of the complex nature of antitumour immune responses, a number of therapies may be required for complete tumour eradication and generation of systemic immunity. We report here the improved antitumour effect of two cytokines, interleukin-2 (IL-2) and interleukin-12 (IL-12), when coexpressed by neuroblastoma cell lines. Initially, transfection of human and mouse neuroblastoma cell lines resulted in high expression levels of biologically active IL-2 and IL-12 in vitro. These cytokines when expressed by transfected Neuro-2A cells completely abolished their in vivo tumorigenicity in a syngeneic neuroblastoma model. Vaccination of established tumours with IL-12-producing cells exhibited a clear effect with reduced tumour growth in the presence of IL-2. In vivo depletion studies showed that CD4(+) and CD8(+) T cells mediate the response against cytokine-producing cells. These results suggest that IL-2 and IL-12, when cotransfected in tumour cells, are effective against established disease and provide a promising immunotherapeutic approach for the treatment of neuroblastoma.

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Citations

Aug 31, 2011·Journal of Oncology·Subhasree Roy ChoudhurySwapan K Ray
Mar 26, 2015·Immunotherapy·Michela CroceSilvano Ferrini
Jul 11, 2009·Pediatric Blood & Cancer·Juliet C Gray, Janice A Kohler
Feb 4, 2010·Cell Biology and Toxicology·Stephen L Hart
May 17, 2019·Immunotherapy·Parnian JabbariNima Rezaei
Mar 6, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Stephanie M GrosseStephen L Hart
Feb 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yoshiki KatsumiTohru Sugimoto

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Methods Mentioned

BETA
surgical resection
transfection
phage display
fluorescence-activated cell sorting
ELISA
density gradient centrifugation
immunodepletion
transfect
transfections

Software Mentioned

Cell Quest

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