Alphavirus neoantigen vectors and interferon inhibitors
AssigneeSeattle Project Corp.
InventorsKarin Jooss, Amy Rachel Rappaport, Leonid Gitlin
Life of this patent
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Abstract
Disclosed herein are vectors that include alphavirus-based expression platforms. Also disclosed are methods associated with the alphavirus-based expression platforms and co-administration of an inhibitor of Type I interferon signaling.
Claims18
A method for stimulating an immune response in a subject, the method comprising administering to the subject a composition for delivery of an expression system and administering to the subject an inhibitor of Type I interferon signaling,
- wherein the composition for delivery of the expression system comprises the expression system,
- wherein the expression system comprises one or more vectors,
- the one or more vectors comprising:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises the nucleic acid sequence set forth in SEQ ID NO:
- 6, comprising:
- (i) at least one promoter nucleotide sequence, and
- (ii) at least one polyadenylation (poly(A)) sequence;
- and
- (b) a cassette, wherein the cassette comprises:
- (i) at least one nucleic acid sequence, optionally wherein the at least one nucleic acid sequence comprises a polypeptide-encoding nucleic acid sequence, optionally wherein the polypeptide-encoding nucleic acid sequence is an antigen-encoding nucleic acid sequence comprising:
- a. an epitope-encoding nucleic acid sequence, optionally comprising at least one alteration that makes the encoded epitope sequence distinct from the corresponding peptide sequence encoded by a wild-type nucleic acid sequence,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- (ii) optionally, a second promoter nucleotide sequence operably linked to the at least one nucleic acid sequence;
- and
- (iii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus.
A method for stimulating a tumor specific immune response in a subject, the method comprising administering to the subject a composition for delivery of an expression system and administering to the subject an inhibitor of Type I interferon signaling,
- wherein the composition for delivery of the expression system comprises the expression system,
- wherein the expression system comprises one or more vectors,
- the one or more vectors comprising:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises the nucleic acid sequence set forth in SEQ ID NO:
- 6, comprising:
- (i) at least one promoter nucleotide sequence, and
- (ii) at least one polyadenylation (poly(A)) sequence;
- and
- (b) a cassette, wherein the cassette comprises:
- (i) at least one nucleic acid sequence, optionally wherein the at least one nucleic acid sequence comprises a polypeptide-encoding nucleic acid sequence,
- optionally wherein the polypeptide-encoding nucleic acid sequence is an antigen-encoding nucleic acid sequence comprising:
- a. an epitope-encoding nucleic acid sequence, optionally comprising at least one alteration that makes the encoded epitope sequence distinct from the corresponding peptide sequence encoded by a wild-type nucleic acid sequence,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- (ii) optionally, a second promoter nucleotide sequence operably linked to the at least one nucleic acid sequence;
- and
- (iii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus.
A method of enhancing delivery of an alphavirus-based expression system, the method comprising administering to the subject a composition for delivery of an expression system and administering to the subject an inhibitor of Type I interferon signaling,
- wherein the composition for delivery of the expression system comprises the expression system,
- wherein the expression system comprises one or more vectors,
- the one or more vectors comprising:
- (a) an RNA alphavirus backbone, wherein the RNA alphavirus backbone comprises the nucleic acid sequence set forth in SEQ ID NO:
- 6, comprising:
- (i) at least one promoter nucleotide sequence, and
- (ii) at least one polyadenylation (poly(A)) sequence;
- and
- (b) a cassette, wherein the cassette comprises:
- (i) at least one nucleic acid sequence, optionally wherein the at least one nucleic acid sequence comprises a polypeptide-encoding nucleic acid sequence, optionally wherein the polypeptide-encoding nucleic acid sequence is an antigen-encoding nucleic acid sequence comprising:
- a. an epitope-encoding nucleic acid sequence, optionally comprising at least one alteration that makes the encoded epitope sequence distinct from the corresponding peptide sequence encoded by a wild-type nucleic acid sequence,
- b. optionally a 5′ linker sequence, and
- c. optionally a 3′ linker sequence;
- (ii) optionally, a second promoter nucleotide sequence operably linked to the at least one nucleic acid sequence;
- and
- (iii) optionally, at least one second poly(A) sequence, wherein the second poly(A) sequence is a native poly(A) sequence or an exogenous poly(A) sequence to the alphavirus.
Dependencies are inferred from the claim text.