Recombinant pseudocowpoxvirus
Inventors
Rittner, Karola • REMY, Christelle • Thioudellet, Christine
Assignees
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Publication Number
US-12377142-B2
Publication Date
2025-08-05
Expiration Date
Abstract
The present invention is in the field of viral immunotherapy. The invention provides new pseudocowpox (PCPV) viruses, in particular recombinant PCPV, composition thereof as well as their therapeutic use for preventing or treating diseases, and, notably, proliferative diseases like cancers and restenosis and infectious diseases such as chronic ones. The present invention also provides methods for generating and amplifying such a PCPV and a method for eliciting or stimulating and/or re-orienting an immune response using such a PCPV. More specifically, the invention provides an alternative to the existing poxvirus vectors such as MVA (Modified Virus Ankara) and may be largely used for the therapeutic vaccination.
Core Innovation
The invention relates to recombinant pseudocowpoxvirus (PCPV) viral immunotherapy. It provides a vaccine composition comprising a therapeutically effective amount of PCPV in a pharmaceutically acceptable vehicle, where the PCPV genome contains at least one foreign nucleic acid inserted into defined genomic locations and encodes cancer antigens.
The insertion sites are selected from non-essential viral genes, non-coding regions, intergenic regions, portions not encoding gene products, or duplicated loci. In representative embodiments, recombinant PCPV constructs include insertion at a VEGF locus and placement of the foreign nucleic acids under control of vaccinia virus promoters, and the constructs may further comprise immunostimulatory proteins.
The document also describes PCPV variants with defective functions and comparative evaluation versus MVA/VV. Recombinant PCPV induces enhanced innate immune activation relative to comparator viruses, including MOI-dependent IFN-α secretion from human PBMCs and increased moDC activation marker CD86, with reported anti-tumor control and survival in a syngeneic MC38 tumor model.
Claims Coverage
The provided independent claim contains the core vaccine-composition inventive concept with multiple inventive features, including a recombinant PCPV genome with a foreign nucleic acid encoding a cancer antigen and a defined set of permissible insertion sites. Dependent claims refine the PCPV source, promoter control, insertion locus, dose formatting, and exemplified cancer antigen types.
Recombinant PCPV vaccine composition with foreign nucleic acid encoding a cancer antigen
A vaccine composition comprising a therapeutically effective amount of a pseudocowpoxvirus (PCPV) and a pharmaceutically acceptable vehicle; wherein said PCPV comprises at least one foreign nucleic acid inserted in its genome; wherein said at least one foreign nucleic acid encodes a cancer antigen.
Permitted insertion-site selection in the PCPV genome
The insertion site is selected from the group consisting of a non-essential viral gene, an intergenic region, a portion of the PCPV genome which does not encode gene products, and a duplicated locus.
PCPV source strain defined by ATCC reference number
The PCPV component is obtained from the wild-type TJS strain identified by ATCC VR-634 or from a virus strain of the same name or functional variants thereof.
Foreign nucleic acid promoter control using selected vaccinia virus promoters
At least one foreign nucleic acid is placed under control of a specified vaccinia virus promoter selected from listed promoter types including named promoters and promoter classes such as early/late chimeric promoters and synthetic promoters.
VEGF locus insertion
The foreign nucleic acid is inserted into the VEGF locus.
Dose formatting as individual doses in a defined pfu range
The vaccine composition is formulated as individual doses containing approximately 10^3 to approximately 10^12 pfu of PCPV.
Cancer antigen selected from MUC-1, HPV, or HBV
A cancer antigen selected from a MUC-1 antigen, an HPV antigen, or an HBV antigen.
Across the independent and dependent claims, the coverage centers on a recombinant PCPV vaccine composition where a foreign nucleic acid encoding a cancer antigen is inserted into a selectable set of PCPV genomic locations, with further narrowing to specific embodiments such as VEGF locus insertion, promoter control by selected vaccinia virus promoters, a defined PCPV strain source, individual-dose pfu formatting, and exemplary antigen selections including MUC-1, HPV, and HBV.
Stated Advantages
Enhanced innate immune activation versus MVA/VV, including MOI-dependent IFN-α secretion from human PBMCs and increased moDC activation marker CD86.
Conversion of M2 macrophages toward a less suppressive phenotype.
Reduction of MDSC-mediated suppression with restored CTL proliferation and Granzyme B.
Distinct local cytokine/chemokine signatures after injection.
Altered tumor-infiltrating populations, including higher neutrophils and reduced MHC II lo TAMs.
Anti-tumor control and survival improvement in a syngeneic MC38 tumor model.
Improved results with heterologous prime-boost (PCPV/MVA) and combination with anti-PD1 immune checkpoint blockade.
Documented Applications
Therapeutic use of recombinant PCPV viral immunotherapy as a cancer treatment in syngeneic MC38 tumor models, including heterologous prime-boost (PCPV/MVA) and combination with anti-PD1 immune checkpoint blockade.
Therapeutic methods for infectious diseases [procedural detail omitted for safety].
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