Immunogenic compositions containing bacterial outer membrane vesicles and therapeutic uses thereof
Inventors
Grandi, Guido • Cafardi, Valeria • Fantappie′, Laura • Grifantini, Renata • Grandi, Alberto
Assignees
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Publication Number
US-11066453-B2
Publication Date
2021-07-20
Expiration Date
Abstract
The present invention provides means and products for the stimulation of an immune response against tumors in a subject in need thereof. More specifically the invention provides immunogenic compositions containing bacterial outer membrane vesicles loaded with tumor antigens, fusion proteins comprising a bacterial protein and a tumor antigen, and isolated bacterial outer membrane vesicles (OMVs) containing said fusion proteins. The fusion proteins, OMVs and immunogenic compositions according to the invention are used in the prevention and treatment of tumors.
Core Innovation
The invention relates to immunogenic cancer vaccine compositions comprising isolated bacterial outer membrane vesicles (OMVs) engineered to display immunogenic tumor antigen proteins through fusion proteins. The fusion proteins comprise an isolated bacterial protein fused to one or more copies of an immunogenic tumor antigen protein, and the isolated bacterial protein is selected from Neisseria meningitidis factor H binding protein (fHbp), Neisseria meningitidis NHBA, Escherichia coli outer membrane protein-F (OmpF), and Aggregatibacter actinomycetemcomitans factor H binding protein (Aa-fHbp).
The described OMVs deliver tumor-antigen fusions to OMV compartments and expose the tumor antigen on the OMV surface. The tumor antigen protein includes one or more immunogenic tumor antigen proteins, including hEGFRvIII, hFAT-1, and hMUC-1, as well as immunogenic fragments or peptides identified by SEQ ID numbers. Embodiments also describe fusion architectures including tumor antigen fused to a bacterial protein and optional multiple copies and linker arrangements.
The disclosure includes rationale for the immunogenicity of OMVs and describes producing and formulating the engineered OMVs for tumor prevention and/or tumor treatment. Experimental embodiments assert that immunization induces specific antibody responses to the disclosed tumor antigens, with reported localization and confirmation that OMVs incorporate the engineered tumor-antigen fusions, including evidence such as flow cytometry/FACS and Western blot.
Claims Coverage
The independent claims cover two related inventive concepts: (i) an isolated bacterial outer membrane vesicle engineered with a fusion protein containing a selected bacterial protein fused to immunogenic tumor antigen protein copies, and (ii) an immunogenic composition comprising a mixture of such OMVs that differ from each other by which immunogenic tumor antigen protein is included. Across both independent claims, the inventive features are limited to specific bacterial proteins and to immunogenic tumor antigen proteins, including named human antigens and immunogenic fragments.
Engineered isolated bacterial outer membrane vesicle with fusion protein
An isolated bacterial outer membrane vesicle comprising a fusion protein, wherein the fusion protein comprises an isolated bacterial protein fused to one or more copies of an immunogenic tumor antigen protein, wherein the isolated bacterial protein is selected from the group consisting of Neisseria meningitidis factor H binding protein (fHbp), Neisseria meningitidis NHBA, Escherichia coli outer membrane protein-F (OmpF), and Aggregatibacter actinomycetemcomitans factor H binding protein (Aa-fHbp).
Mixture of engineered OMVs differing in tumor antigen included in the fusion protein
An immunogenic composition comprising a mixture of isolated bacterial outer membrane vesicles each comprising a fusion protein, wherein the fusion protein comprises an isolated bacterial protein fused to an immunogenic tumor antigen protein, and wherein each outer membrane vesicle differs from the other in the type of the immunogenic tumor antigen protein comprised in the fusion protein.
Overall, the claim coverage focuses on engineered isolated bacterial outer membrane vesicles bearing fusion proteins that link defined bacterial proteins to immunogenic tumor antigen proteins, with an immunogenic composition aspect that requires a mixture of OMVs that differ by the specific immunogenic tumor antigen protein incorporated in the fusion.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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