IL-12p70 and IL-18 gene-modified dendritic cells loaded with tumor antigen-derived peptides or recombinant protein effectively stimulate specific Type-1 CD4+ T-cell responses from normal donors and melanoma patients in vitro

Cancer Gene Therapy
L VujanovicW J Storkus

Abstract

Although CD4(+) Type-1T helper (Th1) cells secreting interferon-gamma (IFN-gamma) appear to play an essential role in promoting durable antitumor immunity, we have previously shown that patients with cancer exhibit dysfunctional Th1-type responses against epitopes derived from tumor antigens, such as MAGE-A6. Here, we engineered human dendritic cells (DCs) to secrete high levels of the IFN-gamma-inducing cytokines, interleukin (IL)-12p70 and IL-18, via recombinant adenoviral infection to generate an in vitro stimulus capable of promoting previously deficient patient Th1-type responses. Dendritic cells co-infected with Ad.IL-12 and Ad.IL-18 (DC.IL-12/18) were more effective at stimulating MAGE-A6-specific Th1-type CD4(+) T-cell responses than DCs infected with either of the cytokine vectors alone, control Ad.Psi5 virus or uninfected DCs. Furthermore, we show that DC.IL-12/18 loaded with recombinant MAGE-A6 protein (rMAGE) and used as in vitro stimulators promote Th1-type immunity that is frequently directed against multiple MAGE-A6-derived epitopes. The superiority of DC.IL-12/18-based stimulations in melanoma patients was independent of disease stage or current disease status. Based on these results, we believe this modality ma...Continue Reading

References

Jan 1, 1990·Cancer Immunology, Immunotherapy : CII·S K HooverH D Bear
Mar 1, 1997·Journal of Virology·S HardyM L Phipps
Jun 1, 1997·The Journal of Investigative Dermatology·M A LowesG M Halliday
Dec 22, 1998·The Journal of Experimental Medicine·K HungH Levitsky
Aug 19, 2000·Cancer Chemotherapy and Pharmacology·T NishimuraS Nishimura
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·F FallarinoP Puccetti
May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Victor AppayAnthony D Kelleher
Jul 23, 2003·Current Pharmaceutical Design·Guillermo MazzoliniIgnacio Melero
Dec 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ralf GutzmerThomas Werfel
Sep 18, 2004·Clinical and Experimental Immunology·V Appay
Sep 28, 2004·Cancer Immunology, Immunotherapy : CII·Peter HerseyHeather Johnson

❮ Previous
Next ❯

Citations

May 20, 2008·Cancer Immunology, Immunotherapy : CII·Lazar VujanovicLisa H Butterfield
Mar 26, 2010·Breast Cancer Research and Treatment·Ozcan MetInge Marie Svane
Mar 22, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Barbara-ann GuinnAlbert B Deisseroth
Aug 7, 2009·Human Gene Therapy·Evelien L J M SmitsViggo F I Van Tendeloo
Nov 30, 2006·Annual Review of Immunology·Ann M LeenAaron E Foster
Mar 25, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Hetty J BontkesErik Hooijberg
Nov 21, 2007·Surgical Oncology Clinics of North America·Nicole M AgostinoPaul J Mosca
Oct 19, 2006·Seminars in Oncology·Hubert Kübler, Johannes Vieweg
Jan 16, 2007·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·James W YoungDerek N J Hart
Mar 1, 2006·International Journal of Oral and Maxillofacial Surgery·Z WangS Li
Mar 16, 2006·The Journal of Medical Investigation : JMI·Mohammad AlizadehMohammed A Satter
May 16, 2014·World Journal of Clinical Oncology·Monali VasekarChandra P Belani
Nov 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael W LipscombWalter J Storkus
Aug 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yanyan QuWalter J Storkus
Feb 7, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tatiana M Garcia-BatesRobert L Ferris
Sep 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephanie DarmaninMasanobu Kobayashi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cancer Vaccines

Cancer vaccines are vaccines that either treat existing cancer or prevent development of a cancer.