IMMUNOSUPPRESSIVE COMPONENTS ASSOCIATED WITH RETROVIRAL REPLICATING VECTORS
The disclosure provides for one or more immunosuppressive components associated with retroviral replicating vectors (RRVs) that contribute to RRV tumor specificity and efficacy.
1 . An immunosuppressive composition comprising (i) a non-replicating viral-like particle (VLP) comprising structural gag and pol polypeptides from a gammaretrovirus; and/or (ii) a gamma retroviral gag-pol polyprotein.
2 . The composition of claim 1 , wherein the VLP lacks an envelope.
3 . The composition of claim 1 , wherein the VLP lacks a retroviral genome.
4 . The composition of claim 1 , wherein the VLP inhibits IFN-α production.
5 . The composition of claim 1 , wherein the VLP comprises one or more immunosuppressive components associated with a gammaretrovirus that block Type I IFN production and/or reduce tumor cell responses to IFN.
6 . The composition of claim 5 , wherein the one or more immunosuppressive components attenuate the inhibition of a retrovirus in tumor cells and/or attenuate the induction of IFN-regulated genes in response to an infection by the retrovirus.
7 . The composition of claim 5 , wherein the immunosuppressive components block the activation of endosomal Toll-like receptors (TLRs) in pDCs and subsequent induction of Type I IFN production.
8 . A composition comprising a VLP of claim 1 and further comprising an additional immunosuppressive agent.
9 . The composition of claim 8 , wherein the additional immunosuppressive agent is an anti-IFNα antibody or fragment thereof.
10 . The composition of claim 8 , wherein the additional immunosuppressive agent is a steroid.
11 . (canceled)
12 . A method of treating an immune disorder comprising administering to a subject a composition of claim 1 wherein IFNα activity and/or production in inhibited.
13 . The method of claim 12 , wherein the immune disorder is selected from the group consisting of rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis, dermatomyositis, spondyloarthropathies such as ankylosing spondylitis, and Sjogren's syndrome.
14 . The method of claim 13 , wherein the immune disorder is systemic lupus erythematosus.
15 . A method of treating a subject with cancer comprising administering to the subject a composition of claim 1 , prior to administering a recombinant retroviral vector comprising a gene that converts a prodrug to a cytotoxic drug.
16 . The method of claim 12 , wherein the composition further comprises an additional immunosuppressive agent.
17 . The method of claim 15 , wherein the composition further comprises an additional immunosuppressive agent.