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Publication Number
US-11357842-B2
Publication Date
2022-06-14
Expiration Date
Abstract
The present invention relates to an attenuated strain of Salmonella comprising at least one copy of a DNA molecule comprising an expression cassette encoding PD-L1. In particular, the present invention relates to said attenuated strain of Salmonella for use in the treatment of cancer.
Core Innovation
The invention relates to cancer immunotherapy by orally administering an attenuated Salmonella strain comprising a DNA molecule with a eukaryotic expression cassette encoding PD-L1. The PD-L1 comprises an amino acid sequence set forth in SEQ ID NO: 1 or an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 1, and the immunogenicity of PD-L1 having at least 80% sequence identity is reduced by less than 50% compared to the immunogenicity of PD-L1 having the amino acid sequence set forth in SEQ ID NO: 1.
The described approach focuses on inducing PD-L1-specific T-cell responses and antibody responses in gut immune compartments. The document indicates involvement of gut-associated immune locations such as Peyer's patches and Peyer's patch macrophages, and it describes the PD-L1-specific immunogenicity as immunogenic against PD-L1 in the treated context.
The disclosure includes eukaryotic promoter elements, including a CMV promoter, within the DNA expression cassette and PD-L1 sequence variants, including full-length and truncated forms corresponding to extracellular domain variants. The disclosure also describes combination strategies involving chemotherapy and/or radiotherapy and additional Salmonella DNA vaccine components that target tumor antigens and tumor stroma antigens.
Claims Coverage
The independent claim covers a method of treating cancer by oral administration of an attenuated Salmonella strain carrying a PD-L1-encoding eukaryotic expression cassette with specified PD-L1 sequence constraints and an immunogenicity reduction requirement. The independent claim includes five inventive features.
Oral administration of attenuated Salmonella for cancer treatment
Administering orally to the cancer patient an effective amount of an attenuated strain of Salmonella as the therapeutic delivery vehicle.
Eukaryotic expression cassette encoding PD-L1 in Salmonella
Using an attenuated Salmonella strain comprising at least one copy of a DNA molecule comprising a eukaryotic expression cassette that encodes PD-L1.
PD-L1 sequence defined by SEQ ID NO: 1 or ≥80% identity
Defining the PD-L1 encoded by the cassette as comprising an amino acid sequence as set forth in SEQ ID NO: 1 or an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 1.
Immunogenicity reduction criterion for PD-L1 sequence variants
Requiring that immunogenicity of the PD-L1 protein with at least 80% sequence identity is reduced by less than 50% when compared to the immunogenicity of the PD-L1 protein comprising the amino acid sequence set forth in SEQ ID NO: 1.
PD-L1-positive tumor cells and PD-L1-specific immunogenicity
Limiting the treatment to cancers comprising PD-L1-positive tumor cells and requiring that the immunogenicity of the protein is PD-L1-specific immunogenicity.
Overall, the claim coverage centers on oral treatment using an attenuated Salmonella strain carrying a eukaryotic PD-L1 expression cassette, with PD-L1 defined relative to SEQ ID NO: 1 and an explicit constraint that immunogenicity is reduced by less than 50% versus SEQ ID NO: 1, for cancers characterized by PD-L1-positive tumor cells and PD-L1-specific immunogenicity.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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