Abstract: The immune response to melanoma cells and tumors can be induced or significantly increased by administering to a subject a pharmaceutical composition comprising alphavirus particles, especially Venezuelan equine encephalitis virus replicon particles, which express the melanoma antigen dopachrome tautomerase (DCT, TRP2) in cells of the subject, with the result of tumor regression and/or inhibition of metastasis of a melanoma subject, or a decreased risk of the occurrence or recurrence of melanoma and/or decreased severity of melanoma in a subject not suffering from melanoma at the time of administration. The pharmaceutical composition described herein can be used in conjunction with other therapeutic agents, it can be administered on more than one occasion and it can be combined with administrations of other compositions such as protein or other immunogenic compositions, and/or adjuvants, with beneficial effects to the human or animal subject to which it has been administered.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus non-structural proteins.

Abstract: The immune response to melanoma cells and tumors can be induced or significantly increased by administering to a subject a pharmaceutical composition comprising alphavirus particles, especially Venezuelan equine encephalitis virus replicon particles, which express the melanoma antigen dopachrome tautomerase (DCT, TRP2) in cells of the subject, with the result of tumor regression and/or inhibition of metastasis of a melanoma subject, or a decreased risk of the occurrence or recurrence of melanoma and/or decreased severity of melanoma in a subject not suffering from melanoma at the time of administration. The pharmaceutical composition described herein can be used in conjunction with other therapeutic agents, it can be administered on more than one occasion and it can be combined with administrations of other compositions such as protein or other immunogenic compositions, and/or adjuvants, with beneficial effects to the human or animal subject to which it has been administered.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus nonstructural proteins.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus non-structural proteins.

Abstract: The present invention provides an isolated RNA molecule comprising: a) an alphavirus 5? replication recognition sequence, wherein at least one initiation codon has been removed from the 5? replication recognition sequence; b) a nucleotide sequence encoding an alphavirus structural protein; and c) an alphavirus 3? replication recognition sequence, with the proviso that the RNA molecule does not contain a promoter that directs transcription of the nucleotide sequence of (b), and wherein the alphavirus 5? and 3? replication recognition sequences of (a) and (c) direct replication of the RNA molecule in the presence of alphavirus nonstructural proteins.

Abstract: The present invention provides methods and compositions comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from 1) an isolated nucleic acid encoding an env gene product or an immunogenic fragment thereof of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gag gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the gag gene product or immunogenic fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or the immunogenic fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the pol gene product or immunogenic fragment thereof is modified to inhibit protease, integrase, RNase H and/or reverse transcriptase activity, and wherein the nucleic acids are each contained within a separate alphavirus replicon particle.

Abstract: The present invention provides methods and compositions comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from 1) an isolated nucleic acid encoding an env gene product or an immunogenic fragment thereof of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a g&agr;g gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the g&agr;g gene product or immunogenic fragment thereof is modified to inhibit formation of virus-like particles containing the g&agr;g gene product or the immunogenic fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the pol gene product or immunogenic fragment thereof is modified to inhibit protease, integrase, RNase H and/or reverse transcriptase activity, and wherein the nucleic acids are each contained within a separate alphavirus replicon

Abstract: The present invention provides methods and compositions comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from 1) an isolated nucleic acid encoding an env gene product or an immunogenic fragment thereof of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gag gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the gag gene product or immunogenic fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or the immunogenic fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product or an immunogenic fragment thereof of a human immunodeficiency virus, wherein the pol gene product or immunogenic fragment thereof is modified to inhibit protease, integrase, RNase H and/or reverse transcriptase activity, and wherein the nucleic acids are each contained within a separate alphavirus replicon particle.