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E-Poster Display

1061P - TCR and HLA analysis of patients in a phase I/IIa trial of a therapeutic CMV vaccine against recurrent glioblastoma (GBM)

Date

17 Sep 2020

Session

E-Poster Display

Topics

Immunotherapy

Tumour Site

Presenters

David Anderson

Citation

Annals of Oncology (2020) 31 (suppl_4): S645-S671. 10.1016/annonc/annonc279

Authors

D.E. Anderson1, A. Zilberberg2, H. Philip2, M. Gordon2, A. Fluckiger3, S. Efroni2, F. Diaz-Mitoma1

Author affiliations

  • 1 R&d, VBI Vaccines, 2142 - Cambridge/US
  • 2 The Mina & Everard Goodman Faculty Of Life Sciences, Bar Ilan University, 52000 - Ramat Gan/IL
  • 3 Immunology, VBI Vaccines, 2142 - Cambridge/US

Resources

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Abstract 1061P

Background

Cytomegalovirus (CMV) antigens have been reported in over 90% of GBM tumors. We have completed the first portion of an on-going phase I/IIa clinical trial for recurrent GBM patients using CMV gB/pp65 enveloped virus-like particles (eVLPs) formulated with GM-CSF and administered intradermally. We have reported that tumor responses were observed only among Vaccine Responders, based on increases in CMV-specific IFN-g ELISPOT responses, which translated to a 6-month improvement in median overall survival. We evaluated the HLA restriction and TCR repertoires of patients to determine if either correlated with those patients likely to observe tumor response and clinical benefit.

Methods

PBMC samples prior to treatment were available for 17 patients, with a variable number of additional samples obtained from each patient obtained, two weeks after each monthly treatment with VBI-1901. TCR repertoire analysis was performed on a total of 29 PBMC samples from 6 Vaccine Responders (range 3-9 samples/patient, median 4.5) and on 29 PBMC samples from 11 Non-responders (range 1-4 samples/patient, median 3).

Results

Quantitative analysis of the TCR repertoire suggests a trend towards a reduced number of unique CDR3 sequences in the TCR b chain over time in Vaccine Responders vs. Non-Responders, associated with a modest reduction in TCR b chain diversity over time. HLA class I alleles known to present CMV pp65 antigens were present in the majority of patients, regardless of whether they were Vaccine Responders or Non-Responders. Among the 4 patients with tumor responses, the HLA-B*0702 allele, known to present both CMV pp65 and IE-1 peptides, was present in 3/4 patients whereas it was present in only 2/13 patients with progressive disease.

Conclusions

TCR repertoire analysis suggests a narrowing of the T cell repertoire with repeat vaccination, and HLA analysis suggests that epitope spreading to a CMV antigen (IE-1) not contained in VBI-1901 may be associated with tumor responses in patients that respond to the vaccine.

Clinical trial identification

NCT03382977.

Editorial acknowledgement

Legal entity responsible for the study

VBI Vaccines.

Funding

VBI Vaccines.

Disclosure

D.E. Anderson, F. Diaz-Mitoma: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: VBI Vaccines. A-C. Fluckiger: Advisory/Consultancy: VBI Vaccines. All other authors have declared no conflicts of interest.

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