53P - Oncolytic adenovirus expressing tumor neoepitopes as a vaccine (53P)

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Bioethics, Legal, and Economic Issues
Colon Cancer
Rectal Cancer
Presenter Martí Farrera Sal
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors M. Farrera Sal1, R. Moreno1, J. de Sostoa Pomés1, M. Arias-Badia1, C.A. Fajardo1, A. Al-Zaher1, M. Bazan-Peregrino2, R. Alemany1
  • 1Procure, Bellvitge Biomedical Research Institute (IDIBELL) - Hospital Duran i Reynals, 08908 - Hospitalet de Llobregat/ES
  • 2R&d, VCN Biosciences S.L., 08174 - Sant Cugat del Vallès/ES

Abstract

Background

The expression of mutated proteins by tumour cells (neoepitopes) and the detection of tumour-specific cytotoxic T-lymphocytes against these antigens in cancer patients support the interest of using vaccines as antitumor treatments. The aim of this study is to assess the possibility of using oncolytic adenovirus (OAds) coding for a patient’s specific neoepitopes as an “oncolytic personalized vaccine”.

Methods

A murine melanoma cell line (B16) was exome-sequenced to select tumor’s neoepitopes. They were selected and prioritized according to their expression levels and predicted MHC-I affinity. Five 27mer peptides including the selected amino acid change in position 14 and a control OVA257 were set up in a Tandem-Minigene (TMG) configuration with or without Gly-Ser linkers. The correspondent mRNA sequence for TMG was incorporated by recombineering as a transgene after the fiber in an OAd (ICO15 with an E3 6.7/19K deletion) regulated by cytomegalovirus promoter (CMV).

Results

The OAd expressing tumour neoepitopes with (ICO15-del6.7/19K-CMV-SpB16TMG.Linkers) or without linkers (ICO15-del6.7/19K-CMV-SpB16TMG) via TMG were successfully generated and purified. We confirmed that they retain the oncolytic potency of its parental virus and that the control OVA257 included in the TMG could be presented via H2-Kb (murine MHC-I) by murine dendritic cell line. Mice were injected with 3e10 viral particles intravenously and ELISPOT was performed 7 days later to assess the capability to induce an immune response against the encoded neoepitopes. Positive peptide controls E1B and OVA257 confirmed a good virus immunization and transgene expression respectively by both viruses. Tumour neoepitopes expressed with linkers presented fewer capacity of inducing immune responses compared to the TMG without linkers. In fact, a clear immune response was detected against a previously published neoepitope (TNPO3, G504A) with similar levels as E1B and OVA257 when expressed by the OAd in the absence of linkers. In vivo efficacy will be assessed.

Conclusions

OAds expressing tumour neoepitopes via TMG induce an immune response against those neoepitopes in vivo. Linkers in a TMG reduces the intensity of the immune response against encoded neoepitopes compared to TMG without linkers expressed by OAds.

Clinical trial identification

Legal entity responsible for the study

Bellvitge Biomedical Research Institute (IDIBELL) and VCN Biosciences S.L.

Funding

Bellvitge Biomedical Research Institute (IDIBELL) and VCN Biosciences S.L.

Disclosure

M. Farrera Sal: Industrial phD student, perfoming it in academic group (Virotherapy and Immunotherapy group, IDIBELL) and biotechnological company (VCN Biosciences S.L.)

All other authors have declared no conflicts of interest.