Tumor protection following vaccination with low doses of lentivirally transduced DCs expressing the self-antigen erbB2

Molecular Therapy : the Journal of the American Society of Gene Therapy
Miriam E MossobaJeffrey A Medin

Abstract

Gene therapy strategies may accelerate the development of prophylactic immunotherapy against cancer. We synthesized a lentiviral (LV) vector encoding a kinase-deficient form of erbB2 (erbB2tr) to transduce murine dendritic cells (DCs) efficiently. Murine erbB2 models a clinically relevant tumor-associated self-antigen; its human homolog (HER-2/neu) is overexpressed in breast cancer and in 80% of metastatic prostate cancers. Following one infection, approximately 47% of DCs overexpressed erbB2tr. To determine whether low doses of transduced DCs could protect mice from prostate cancer cells, we performed prime/boost vaccinations with 2 x 10(3) or 2 x 10(5) erbB2tr-transduced DCs. Six weeks after vaccination, mice were simultaneously bilaterally challenged with the aggressive RM-1 prostate cancer cell line and an erbB2tr-expressing variant (RM-1-erbB2tr). Whereas control mice developed both tumors, all recipients of 2 x 10(5) erbB2tr-transduced DCs developed only wild-type RM-1 tumors. One-third of mice vaccinated with just 2 x 10(3) erbB2tr-transduced DCs also demonstrated erbB2tr-specific tumor protection. Protection against RM-1-erbB2tr tumors was associated with sustained levels of anti-erbB2tr antibody production and also cor...Continue Reading

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Citations

Apr 7, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jeanette E BoudreauYonghong Wan
Jul 23, 2013·Virology Journal·James C M WangJeffrey A Medin
Oct 12, 2010·Clinical & Developmental Immunology·Joel F AldrichRonald C Kennedy
Nov 10, 2009·Veterinary Immunology and Immunopathology·Mauro PistelloGiulia Freer
Jan 5, 2011·Immunological Reviews·Biliang HuPin Wang
Mar 26, 2015·Immunotherapy·Robyn Aa OldhamJeffrey A Medin
Mar 12, 2010·Expert Review of Vaccines·Mudita PinchaRenata Stripecke

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