Oncotarget

Research Papers: Immunology:

Using lymph node swelling as a potential biomarker for successful vaccination

Kimberly D. Brewer _, Drew R. DeBay, Iulia Dude, Christa Davis, Kerry Lake, Cathryn Parsons, Rajkannan Rajagopalan, Genevieve Weir, Marianne M. Stanford, Marc Mansour and Chris V. Bowen

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Oncotarget. 2016; 7:35655-35669. https://doi.org/10.18632/oncotarget.9580

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Abstract

Kimberly D. Brewer1,2,3, Drew R. DeBay1, Iulia Dude1, Christa Davis1, Kerry Lake1, Cathryn Parsons1, Rajkannan Rajagopalan4, Genevieve Weir4, Marianne M. Stanford4,5, Marc Mansour4 and Chris V. Bowen1,2,3,6

1 Biomedical Translational Imaging Centre (BIOTIC), Halifax, NS, Canada

2 Department of Radiology, Dalhousie University, Halifax, NS, Canada

3 Department of Physics, Dalhousie University, Halifax, NS, Canada

4 Immunovaccine Inc., Halifax, NS, Canada

5 Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada

6 School of Biomedical Engineering, Dalhousie University, Halifax, NS, Canada

Correspondence to:

Kimberly D. Brewer, email:

Keywords: magnetic resonance imaging; cancer; vaccines; biomarker; emulsion; Immunology and Microbiology Section; Immune response; Immunity

Received: February 17, 2016 Accepted: May 12, 2016 Published: May 24, 2016

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.


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