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Augmenting and broadening T-cell responses to glioblastoma - therapeutic vaccine platform based on HCMV expressing NKG2D ligands

Project description

Vaccination against glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive brain tumour. Several studies have shown the presence of human cytomegalovirus (HCMV) nucleic acids and proteins in GBM tissue. With the rationale that HCMV is implicated in GBM pathology, the EU-funded GLIOVACC project proposes a vaccination strategy that employs a genetically modified HCMV-based vector that carries tumour antigens. Researchers will test the vaccine in a humanised mouse model of GBM and determine the specific immune responses. The study will offer hope for the treatment of GBM, which is characterised by very poor survival.

Objective

The development of an effective vaccine against human cancers is of tremendous importance. Glioblastoma multiforme (GBM) is the most malignant form of brain tumor with extremely poor survival. The human cytomegalovirus (HCMV) is involved in GBM pathogenesis suggesting that viral proteins might provide therapeutic targets. We propose a vaccination strategy against GBM based on a genetically modified HCMV that could target HCMV, as well as tumor specific antigens. The proposal builds on the successful implementation of the ERC-AdG StAdvInn, which investigates a murine cytomegalovirus (MCMV) expressing the NKG2D ligand RAE-1γ (RAE-1γMCMV), which has tremendous potential for strengthening the CD8 T cell response to a vectored antigen (Trsan et al, PNAS 2013). We have shown the strong potential of such vector to act as a CD8 T cell-based vaccine against malignant tumors (Trsan et al, Eur J Immunol 2017). Moreover, the efficiency of this vector can be enhanced by blocking immune checkpoints. We have constructed HCMV expressing the human NKG2D ligand ULBP2 (HCMV/ULBP2) and confirmed its efficacy in vitro and in humanized mice (Tomic et al, PLoS Pathog 2016). Here we propose to determine the capacity of the HCMV/ULBP2 vector in the immune control of GBM. In short, immune cells from GBM patients will be transferred to NSG mice that will be grafted with GBM from the same patients. Mice will be vaccinated with HCMV/ULBP2 vector expressing GBM associated neoantigens. Based on results with the RAE-1γMCMV in the melanoma model and with HCMV/ULBP2 in NSG humanized mice, we expect a strong effector CD8 T cell response to be generated in these mice resulting in the control of tumor in the NSG host. The proposed project activities include: development and validity testing of the prototype of the integrated vaccine vector, implementation of IPR protection and exploitation strategy. The results of this project will be used to establish the first in man trial in GBM bearing patients.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-POC - Proof of Concept Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2018-PoC

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Host institution

SVEUCILISTE U RIJECI, MEDICINSKI FAKULTET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 149 968,00
Address
BRACE BRANCHETTA 20
51000 Rijeka
Croatia

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Region
Hrvatska Jadranska Hrvatska Primorsko-goranska županija
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 149 968,00

Beneficiaries (1)

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