title: Using MRI to evaluate and predict therapeutic success from depot-based cancer vaccines.
abstract: In the preclinical development of immunotherapy candidates, understanding the mechanism of action and determining biomarkers that accurately characterize the induced host immune responses is critical to improving their clinical interpretation. Magnetic resonance imaging (MRI) was used to evaluate in vivo changes in lymph node size in response to a peptide-based cancer vaccine therapy, formulated using DepoVax (DPX). DPX is a novel adjuvant lipid-in-oil-based formulation that facilitates enhanced immune responses by retaining antigens at the injection site for extended latencies, promoting increased potentiation of immune cells. C57BL/6 mice were implanted with C3 (HPV) tumor cells and received either DPX or control treatments, 5 days post-implantation. Complete tumor eradication occurred in DPX-vaccinated animals and large volumetric increases were observed in the vaccine-draining right inguinal lymph node (VRILN) in DPX mice, likely corresponding to increased localized immune response to the vaccine. Upon evaluating the relative measure of vaccine-potentiated immune activation to tumor-induced immune response (VRILN/VLILN), receiver-operating characteristic (ROC) curves revealed an area under the curve (AUC) of 0.90 (±0.07), indicating high specificity and sensitivity as a predictive biomarker of vaccine efficacy. We have determined that for this tumor model, early MRI lymph node volumetric changes are predictive of depot immunotherapeutic success.
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC) , Halifax, Nova Scotia, Canada.
authors.forename: Drew R
authors.initials: DR
authors.lastname: DeBay
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, Nova Scotia, Canada; Immunovaccine Inc., Halifax, Nova Scotia, Canada; Department of Radiology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Brewer
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC) , Halifax, Nova Scotia, Canada.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: LeBlanc
authors.affiliation: Immunovaccine Inc. , Halifax, Nova Scotia, Canada.
authors.forename: Genevieve M
authors.initials: GM
authors.lastname: Weir
authors.affiliation: Immunovaccine Inc. , Halifax, Nova Scotia, Canada.
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Stanford
authors.affiliation: Immunovaccine Inc. , Halifax, Nova Scotia, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, Nova Scotia, Canada; Department of Radiology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Chris V
authors.initials: CV
authors.lastname: Bowen