Cross-presentation of a human tumor antigen delivered to dendritic cells by HSV VP22-mediated protein translocation

European Journal of Immunology
Arvind ChhabraDavid I Dorsky

Abstract

Dendritic cells (DC) capture antigens from apoptotic and/or necrotic tumor cells and cross-present them to T cells, and various ways of delivering tumor antigens to DC in vitro and in vivo are being pursued. Since fusions of antigenic proteins with the HSV integument protein VP22 are capable of intercellular trafficking, this approach has been exploited for delivery of antigens to antigen-presenting cells. Adenoviral vectors were used to express the tumor-associated-but-self-antigen MART-1 fused to HSV VP22 in MART-1-negative A375 melanoma cells and in DC. When expressed in A375 cells and allowed to spread to DC across a transwell barrier, the VP22-MART-1 fusion protein localized to both early and late endosomal structures of the DC. The DC loaded with the VP22-MART-1 fusion by intercellular trafficking efficiently presented the MART-1(27-35) epitope to MART-1(27-35)-specific CTL. Furthermore, transloaded DC were capable of expanding the population of MART-1(27-35)-specific CTL. Thus, a tumor antigen acquired by intercellular trafficking can be cross-presented by DC. This experimental approach should therefore be useful not only for studying the mechanism of cross-presentation but also for vaccine development.

Citations

Jun 16, 2010·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Swagatam RayUNKNOWN UCLA-CALTECH-CHLA-USC-UCONN Consortium on Translational Program in Engineered Immunity
Apr 22, 2008·Veterinary Immunology and Immunopathology·R Curtis BirdBruce F Smith
Feb 6, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Arvind ChhabraBijay Mukherji
Dec 24, 2008·Vaccine·David N PosnettAlan N Houghton
Mar 17, 2010·International Journal of Cancer. Journal International Du Cancer·Kozo Ohkusu-TsukadaMasahiro Toda
Jan 25, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arvind ChhabraDeepika Batra
Aug 13, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arvind Chhabra, Bijay Mukherji
Jul 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arvind ChhabraBijay Mukherji
Nov 4, 2005·Cancer Research·Ramesh B BatchuFrits van Rhee

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