PMID: 26770347Jan 16, 2016Paper

DC targeting DNA vaccines induce protective and therapeutic antitumor immunity in mice

International Journal of Clinical and Experimental Medicine
Qun WangGuang-Fa Zhao

Abstract

Anti-CD11c antibodies target to the CD11c receptor that mediates antigen presentation to T cells by dendritic cells (DCs). To exploit these properties for immunization purposes, we obtained DC-targeting DNA vaccines by fusing tumor-associated antigen HER2/neu ectodomain to single chain antibody fragment (scFv) from N418 (scFv(N418)), a monoclonal antibody binding the mouse DC-restricted surface molecule CD11c, and explored its antitumoral efficacy and underlying mechanisms in mouse breast cancer models. Induction of humoral and cellular immune responses and antitumoral activity of the DNA vaccines were tested in transplantable HER2/neu-expressing murine tumor models and in transgenic BALB-neuT mice developing spontaneous Neu-driven mammary carcinomas. Upon injection of the breast tumor cell line D2F2/E2 (stably expressing human wild-type HER2), scFv(N418)-HER2 immunized mice were protected against tumor growth. Even more important for clinical applications, we were able to substantially slow the growth of implanted D2F2/E2 cells by injection of scFv(N418)-HER2 conjugates into tumor bearing hosts. The existing tumors were eradicated by treatment with scFv(N418)-HER2 combined with low-dose cyclophosphamide (CTX), which can make a...Continue Reading

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