29P - Therapeutic vaccination against glioblastoma multiformae using CMV gB/pp65 eVLPs formulated with GM-CSF

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Cancer Immunology and Immunotherapy
Central Nervous System Malignancies
Presenter David Anderson
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors D.E. Anderson, C. Soare, J. Bozic, B. Ontsouka, T. Ahmed, A. Diress, M. Yorke, A. Fluckiger, M. Kirchmeier
  • Research, VBI Vaccines, 02142 - Cambridge/US

Abstract

Aim

Glioblastoma multiformae (GBM) is presently an incurable brain tumor with 75% of patients dead two years after diagnosis. Approximately 15,000 new GBM diagnoses arise in the USA each year, and 2-3 people/100,000 each year in most European countries. A limitation of past immunotherapeutic vaccines against GBM has been the difficulty in inducing a potent tumor-specific response, due at least in part to the inherently poor immunogenicity of tumor-associated antigens, the means of formulation/delivery of the vaccine, or a combination of both. Human cytomegalovirus (CMV) is a ubiquitous, generally asymptomatic virus that is present in over 90% of GBM tumors. Memory CD4+ and CD8+ T cells are most frequently directed against the gB and pp65 antigens, respectively. Thus, CMV gB and pp65 represent attractive new “neoantigen” components of a vaccine against GBM. Indeed, a phase I clinical trial based on dendritic cell vaccination against CMV pp65 demonstrated a significant improvement in overall survival, and identified the chemokine CCL3 as a correlate of efficacy.

Methods

We are developing a novel enveloped virus-like particle (eVLP) vaccine for treatment of GBMs. Our eVLPs are produced after transfection of HEK 293 cells with plasmid encoding murine leukemia virus (MLV) Gag plasmid fused in-frame with the CMV pp65 antigen, which gives rise to the particles. Plasmid expressing CMV gB antigen is co-transfected such that particles budding from the surface of the cells incorporate the gB protein into the lipid bilayer while the CMV pp65 antigen remains internal to the particles. Pilot (10L) scale production at a GMP-compliant CMO is underway.

Results

Using peripheral blood mononuclear cells (PBMCs) from healthy subjects, we have found that gB/pp65 eVLPs restimulate IFN-g-secreting CD4+ and CD8+ T cells in all subjects examined (n = 8) at mean frequencies of 0.27% and 1.28%, respectively. When formulated with GM-CSF, gB/pp65 eVLP stimulation of PBMCs from healthy subjects (n = 4) and GBM patients (n = 4) induces both IFN-g and CCL3 secretion at comparable levels between these groups.

Conclusions

A mouse study is underway to determine optimal doses, route of administration, and formulation of GM-CSF and eVLPs. A pre-IND meeting is planned with FDA in Q4 2015.

Clinical trial identification

Disclosure

D.E. Anderson, C. Soare, J. Bozic, B. Ontsouka, T. Ahmed, A. Diress, M. Yorke, A.-C. Fluckiger, M. Kirchmeier: Are employees or consultants to VBI Vaccines, Inc. and received salary and in some cases stock option grants. The vaccine candidate described in this abstract is being developed and sponsored by VBI Vaccines.