Periodic Reporting for period 1 - GLIOVACC (Augmenting and broadening T-cell responses to glioblastoma - therapeutic vaccine platform based on HCMV expressing NKG2D ligands)
Reporting period: 2018-12-01 to 2020-07-31
The development of an effective vaccine against human cancers, particularly highly malignant ones as glioblastoma multiforme (GBM), is of tremendous importance. Since it has been shown that human cytomegalovirus (HCMV) is involved in GBM pathogenesis, we have proposed a vaccination strategy against it based on a genetically modified HCMV that could target both HCMV and tumor specific neoantigens. Our vaccine proposal was grounded on the promising results obtained with murine cytomegalovirus (MCMV) expressing the NKG2D ligand RAE-1γ that was shown previously by our group to act as a CD8 T cell-based vaccine against malignant tumors. Therefore, in frame of this PoC, we have successfully constructed HCMV expressing the human NKG2D ligand ULBP2 (HCMV/ULBP2) and GBM associated neoantigens IDH1 and EGFRvIII. We also established patient-derived orthotropic xenograft model of glioblastoma in humanized mice model by engrafting immunodeficient NSG mice with primary GBM cells intracranially, following “humanization” with autologous PBMCs. This model was established to test efficacy of indicated viruses in vivo, via vaccination with autologous moDCs infected with recombinant viruses. The specificity of the proposed platform and animal model is that it allows assessing the response of patient's immune cells and their capacity to control autologous tumors in vivo. Our preliminary data show moderate phenotype in terms of smaller tumors and higher number of immune infiltrates in vaccinated groups compared to mock, but this needs further experimental confirmation. In addition, project activities included implementation of IPR protection and exploitation strategy where we filed a provisional and subsequently a PCT patent application (“Integrated human cytomegalovirus / glioblastoma vaccine”, PCT/IB2020/056946) as well as conducted preliminary survey for patentability). We also initiated thorough search for strategic partners for further development and commercial exploitation of the invention, by preparing, distributing and presenting a pitch deck presentation to various investors in EU and Israel.