Methods and compositions for attenuating gene expression modulating anti-viral transfer vector immune responses
Provided herein are methods and related compositions for administering viral transfer vectors and antigen-presenting cell targeted immunosuppressants.
1. A method comprising:
attenuating an anti-gene expression modulating viral transfer vector response, wherein the anti-gene expression modulating viral transfer vector response is a T cell response, by first administering to a subject a gene expression modulating viral transfer vector without an antigen-presenting cell targeted immunosuppressant, and
subsequently concomitantly administering the gene expression modulating viral transfer vector and an antigen-presenting cell targeted immunosuppressant to the subject.
2. The method of claim 1 , further comprising administering to the subject one or more repeat doses of the viral transfer vector subsequent to the concomitant administration of the viral transfer vector and the antigen-presenting cell targeted immunosuppressant to the subject.
3. A method comprising:
repeatedly, concomitantly administering to a subject an antigen-presenting cell targeted immunosuppressant and gene expression modulating transfer vector, and
selecting one or more doses of the gene expression modulating viral transfer vector to be less than the dose of the gene expression modulating viral transfer vector that would be selected for the subject if the subject were expected to develop anti-gene expression modulating viral transfer vector immune responses due to the repeated administration of the gene expression modulating viral transfer vector.
4. The method of claim 1 , wherein the concomitant administration is simultaneous administration.
5. The method of claim 1 , wherein the subject is one to which the viral transfer vector has not been previously administered.
6. The method of claim 1 , wherein the viral transfer vector is a retroviral transfer vector, an adenoviral transfer vector, a lentiviral transfer vector or an adeno-associated viral transfer vector.
7. The method of claim 1 , wherein the gene expression modulating transgene encodes a DNA-binding protein or a therapeutic RNA.
8. The method of claim 1 , wherein the antigen-presenting cell targeted immunosuppressant comprises an erythrocyte-binding therapeutic.
9. The method of claim 1 , wherein the antigen-presenting cell targeted immunosuppressant comprises a negatively-charged particle.
10. The method of claim 1 , wherein the antigen-presenting cell targeted immunosuppressant comprises an apoptotic-body mimic and one or more viral transfer vector antigens.
11. The method of claim 1 , wherein the antigen-presenting cell targeted immunosuppressant comprises synthetic nanocarriers comprising an immunosuppressant.
12. The method of claim 1 , wherein the immunosuppressant is an inhibitor of the NF-kB pathway.
13. The method of claim 1 , wherein the immunosuppressant is rapamycin.
14. A method comprising:
repeatedly, concomitantly administering to a subject an antigen-presenting cell targeted immunosuppressant and gene expression modulating transfer vector, and
selecting one or more doses of the gene expression modulating viral transfer vector to be at least equal to the dose of the gene expression modulating viral transfer vector that would be selected for the subject if the subject were expected to develop anti-gene expression modulating viral transfer vector immune responses due to the repeated administration of the gene expression modulating viral transfer vector.