The human probiotic strains E. coli Nissle and Lactococcus lactis were successfully engineered with the MHC I epitope OVA. When administered to mice, the engineered strains were shown to elicit OVA specific T cells. Moreover, and importantly, if the animals were subsequently challenged with a tumor cell line expressing OVA the tumor growth was strongly inhibited. Since the engineered probiotic E. coli Nissle releases Outer Membrane Vesicles (OMVs), we also tested whether the OMVs could play a role in the elicitation of the epitope-specific T cells and in protection against tumor challenge. Indeed, the oral administration of OMVs carrying the OVA epitope promoted tumor inhibition in challenged animals. Importantly, we also demonstrated that OMVs decorated with MHC I epitopes other than OVA induced epitope-specific T cells, indicating that T cell production is a general property of intestinal OMVs. This is a particularly interesting result in that it sheds light on a new biological OMV function never reported before.
In a parallel study, we orally administered the probiotic Bifidobacterium and we found that the administration resulted in a perturbation of the intestinal flora. When mice were challenged with a tumor cell line, the animals appeared to be more resistant to tumor development. In line with the MM hypothesis, we discovered that such resistance was associated to the presence of new intestinal microbial species, which carried proteins homologous to immunogenic epitopes present in the tumor cells.
The results of the Vaccibiome project described above, as well as other related data generated thanks to the Vaccibiome financial support, were made publicly available through five publications in international, peer-reviewed, journals and also but oral communications at conferences and seminars at which the PI of the project participated as invited speaker. Other publications will be submitted soon.
The translational value of the project can be appreciated by the fact that a Proof-of-Concept ERC Grant (INSITUOMVAC) was assigned to the PI of the project in June 2023 and the PI is currently looking for additional funding to bring a novel OMV-based immunotherapeutic formulation to development.
