Immune checkpoint inhibitor co-expression vectors

A pharmaceutical composition comprising:

• i. a vector system comprising:
• a. an antigen cassette, the antigen cassette comprising:
• (1) at least one antigen-encoding nucleic acid sequence associated with a tumor present within a subject comprising:
• at least one antigen-encoding nucleic acid sequence, optionally the at least one antigen-encoding nucleic acid sequence comprising an MHC class I antigen-encoding nucleic acid sequence, each comprising:
• a. an epitope encoding nucleic acid sequence, optionally comprising at least one alteration that makes the encoded peptide 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;
• (2) at least one promoter sequence operably linked to at least one antigen-encoding nucleic acid sequence,
• (3) optionally, at least one MHC class II antigen-encoding nucleic acid sequence;
• (4) optionally, at least one GPGPG linker sequence (SEQ ID NO:56);
• (5) optionally, at least one polyadenylation sequence;
• and
• b. a nucleic acid sequence, optionally within the antigen cassette, encoding at least one immune modulator, optionally wherein the nucleic acid sequence encoding the at least one immune modulator is transcribed on:
• (1) the same transcript as the at least one antigen-encoding nucleic acid sequence with an internal ribosome entry sequence (IRES) sequence separating the sequences encoding the at least one immune modulator and the at least one antigen-encoding nucleic acid sequence, or
• (2) a different transcript as the at least one antigen-encoding nucleic acid sequence, wherein at least one second promoter sequence is operably linked to the sequences encoding the at least one immune modulator;
• and
• ii. a pharmaceutically acceptable carrier, optionally wherein
• the pharmaceutical composition further comprises an adjuvant;
• and/or
• the pharmaceutical composition further comprises an immune modulator, optionally wherein the immune modulator is an anti-CTLA4 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, an anti-PD-L1 antibody or an antigen-binding fragment thereof, an anti-4-1BB antibody or an antigen-binding fragment thereof, or an anti-OX-40 antibody or an antigen-binding fragment thereof.

A method for treating a subject with cancer, the method comprising administering to the subject a vector system comprising:

• a. an antigen cassette, the antigen cassette comprising:
• (1) at least one antigen-encoding nucleic acid sequence associated with a tumor present within a subject comprising:
• at least one antigen-encoding nucleic acid sequence, optionally the at least one antigen-encoding nucleic acid sequence comprising an MHC class I antigen-encoding nucleic acid sequence, each comprising:
• a. an epitope encoding nucleic acid sequence, optionally comprising at least one alteration that makes the encoded peptide 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;
• (2) at least one promoter sequence operably linked to at least one antigen-encoding nucleic acid sequence,
• (3) optionally, at least one MHC class II antigen-encoding nucleic acid sequence;
• (4) optionally, at least one GPGPG linker sequence (SEQ ID NO:56);
• (5) optionally, at least one polyadenylation sequence;
• and
• b. a nucleic acid sequence, optionally within the antigen cassette, encoding at least one immune modulator, optionally wherein the nucleic acid sequence encoding the at least one immune modulator is transcribed on:
• (1) the same transcript as the at least one antigen-encoding nucleic acid sequence with an internal ribosome entry sequence (IRES) sequence separating the sequences encoding the at least one immune modulator and the at least one antigen-encoding nucleic acid sequence, or
• (2) a different transcript as the at least one antigen-encoding nucleic acid sequence, wherein at least one second promoter sequence is operably linked to the sequences encoding the at least one immune modulator, and
• optionally wherein:
• a) the vector or composition is administered intramuscularly (IM), intradermally (ID), or subcutaneously (SC);
• and/or
• b) the method further comprises administering to the subject an immune modulator, optionally wherein the immune modulator is administered before, concurrently with, or after administration of the vector or pharmaceutical composition,
• optionally wherein the immune modulator is an anti-CTLA4 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, an anti-PD-L1 antibody or an antigen-binding fragment thereof, an anti-4-1BB antibody or an antigen-binding fragment thereof, or an anti-OX-40 antibody or an antigen-binding fragment thereof;
• or
• wherein the immune modulator is administered intravenously (IV), intramuscularly (IM), intradermally (ID), or subcutaneously (SC), optionally wherein the subcutaneous administration is near the site of the vector or composition administration or in close proximity to one or more vector or composition draining lymph nodes;
• and/or
• c) wherein the method further comprises administering to the subject a second vaccine composition, optionally wherein the second vaccine composition is administered prior to the administration of the vector or the pharmaceutical composition, or wherein the second vaccine composition is administered subsequent to the administration of the vector or the pharmaceutical composition,
• optionally wherein the second vaccine composition is the same as the vector or the pharmaceutical composition or wherein the second vaccine composition is different from the vector or the pharmaceutical composition,
• optionally wherein the second vaccine composition comprises a chimpanzee adenovirus vector, optionally wherein the chimpanzee adenovirus vector is a ChAdV68 vector, or an srRNA vector, optionally wherein the srRNA vector is a Venezuelan equine encephalitis virus vector, optionally wherein the chimpanzee adenovirus vector or the srRNA vector comprises a nucleic acid sequence encoding at least one immune modulator,
• optionally wherein the at least one antigen-encoding nucleic acid sequence encoded by the chimpanzee adenovirus vector or the srRNA vector is the same as the at least one antigen-encoding nucleic acid sequences of any of the above vector claims, and optionally wherein the nucleic acid sequence encoding the at least one immune modulator encoded by the chimpanzee adenovirus vector or the srRNA vector is the same as the at least one immune modulator of any of the above claims.