Polymersomes comprising a soluble encapsulated antigen as well as methods of making and uses thereof
Inventors
Nallani, Madhavan • Decaillot, Fabien • CORNELL, THOMAS ANDREW • KHAN, Amit Kumar
Assignees
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Abstract
The present invention relates to polymersomes comprising a soluble encapsulated antigen, wherein said soluble encapsulated antigen is selected from the group consisting of: a polypeptide, a carbohydrate, a polynucleotide and combinations thereof. The present invention further relates to a method for production of encapsulated antigens in a polymersome as well as to polymersomes produced by said method. The present invention further relates to compositions comprising a polymersome of the present invention, isolated antigen presenting cells or hybridoma cells exposed to the polymersome or composition of the present invention. The present invention also relates to vaccines comprising polymersomes of the present invention, methods of eliciting an immune response or methods for treatment, amelioration, prophylaxis or diagnostics of a cancer, autoimmune or infectious disease, comprising providing polymersomes of the present invention.
Core Innovation
The invention relates to oxidation-stable polymersomes that encapsulate soluble antigens within a lumen of a polymersome membrane, wherein the polymersome membrane comprises a poly(butadiene)-poly(ethylene oxide) (PB-PEO) diblock copolymer amphiphilic polymer. The polymersomes are described as having a diameter ranging from about 100 nm to about 1 μm and as oxidation-stable systems. The encapsulated antigens are described as soluble polypeptides, carbohydrates, and polynucleotides (DNA or mRNA).
The polymersomes are described as eliciting immune responses, including CD8(+) T cell-mediated immune responses to the encapsulated antigen, with cross-presentation. The disclosure contrasts oxidation-stable polymersomes with oxidation-sensitive systems by emphasizing oxidation-stable behavior and oxidation-independent release. Oxidation-stable is described in terms of oxidation stability assessed by hydrogen peroxide (H2O2) release assays and the resulting oxidation-independent content release in serum and endosomal contexts.
The disclosed polymersome system is further characterized and related to vaccine uses by defining polymersome properties and antigen targets. Representative polypeptide antigen targets include ovalbumin (OVA), influenza HA, PEDv spike fragments, and cancer neoantigens such as B16 and MC38 peptides, as well as eGFP DNA. The disclosed applications include administration as vaccines for cancer, autoimmune, and infectious diseases.
Claims Coverage
The provided independent claim family coverage centers on a single independent claim (clm-00001) directed to an oxidation-stable polymersome that encapsulates a soluble polypeptide antigen and elicits a CD8(+) T cell-mediated immune response. The claim includes four main inventive feature groupings.
Oxidation-stable polymersome with encapsulated soluble polypeptide antigen
An oxidation-stable polymersome comprising a soluble polypeptide antigen encapsulated within a lumen of the polymersome formed by an enclosing polymersome membrane.
PB-PEO diblock copolymer membrane
The polymersome membrane comprises a poly(butadiene)-poly(ethylene oxide) (PB-PEO) diblock copolymer amphiphilic polymer, wherein said PB-PEO diblock copolymer comprises a poly(butadiene)21-poly(ethylene oxide)14 diblock.
Polymersome diameter within a defined range
Said polymersome has a diameter ranging from about 100 nm to about 1 μm.
Elicits CD8(+) T cell-mediated immune response
Said polymersome is capable of eliciting a CD8(+) T cell-mediated immune response to the polypeptide antigen.
In the provided claims, the inventive subject matter of clm-00001 is an oxidation-stable PB-PEO polymersome (PB-PEO comprising poly(butadiene)21-poly(ethylene oxide)14) with a defined diameter range that encapsulates a soluble polypeptide antigen and is capable of eliciting a CD8(+) T cell-mediated immune response.
Stated Advantages
Oxidation-stable behavior and oxidation-independent content release in serum and endosomal contexts.
Eliciting immune responses, including CD8(+) T cell-mediated immune responses and cross-presentation.
Documented Applications
Administration as vaccines for cancer, autoimmune, and infectious diseases.
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