title: Using lymph node swelling as a potential biomarker for successful vaccination.
abstract: There is currently a lack of biomarkers to help properly assess novel immunotherapies at both the preclinical and clinical stages of development. Recent work done by our group indicated significant volume changes in the vaccine draining right lymph node (RLN) volumes of mice that had been vaccinated with DepoVaxTM, a lipid-based vaccine platform that was developed to enhance the potency of peptide-based vaccines. These changes in lymph node (LN) volume were unique to vaccinated mice.To better assess the potential of volumetric LN markers for multiple vaccination platforms, we evaluated 100 tumor bearing mice and assessed their response to vaccination with either a DepoVax based vaccine (DPX) or a water-in-oil emulsion (w/o), and compared them to untreated controls. MRI was used to longitudinally monitor LN and tumor volumes weekly over 4 weeks. We then evaluated changes in LN volumes occurring in response to therapy as a potential predictive biomarker for treatment success.We found that for both vaccine types, DPX and w/o, the %RLN volumetric increase over baseline and the ratio of RLN/LLN were strong predictors of successful tumor suppression (LLN is left inguinal LN). The area under the curve (AUC) was greatest, between 0.75-0.85, two (%RLN) or three (RLN/LLN) weeks post-vaccination. For optimized critical thresholds we found these biomarkers consistently had sensitivity >90% and specificity >70% indicating strong prognostic potential. Vaccination with DepoVax had a more pronounced effect on draining lymph nodes than w/o emulsion vaccines, which correlated with a higher anti-tumor activity in DPX-treated mice.
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.|Department of Radiology, Dalhousie University, Halifax, NS, Canada.|Department of Physics, Dalhousie University, Halifax, NS, Canada.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Brewer
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Drew R
authors.initials: DR
authors.lastname: DeBay
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Iulia
authors.initials: I
authors.lastname: Dude
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Christa
authors.initials: C
authors.lastname: Davis
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Kerry
authors.initials: K
authors.lastname: Lake
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Parsons
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada.
authors.forename: Rajkannan
authors.initials: R
authors.lastname: Rajagopalan
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Weir
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada.|Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
authors.forename: Marianne M
authors.initials: MM
authors.lastname: Stanford
authors.affiliation: Immunovaccine Inc., Halifax, NS, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Mansour
authors.affiliation: Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada.|Department of Radiology, Dalhousie University, Halifax, NS, Canada.|Department of Physics, Dalhousie University, Halifax, NS, Canada.|School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada.
authors.forename: Chris V
authors.initials: CV
authors.lastname: Bowen
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D014408:Biomarkers, Tumor / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000276:immunology / Q000628:therapy; D014611:Vaccination / Q000379:methods*
chemical_list: D000276:Adjuvants, Immunologic; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines
keywords: Immune response; Immunity; Immunology and Microbiology Section; biomarker; cancer; emulsion; magnetic resonance imaging (MRI); vaccines