Methods and compositions for localized delivery of agents to virally infected cells and tissues
The invention provides compositions and methods for delivering an agent to virally infected tissues and/or cells of a subject by conjugating agent-loaded nanoparticles to virus-specific T cells, such as cytotoxic T lymphocytes. The agent may be a latency-reversing drug (LRD), an antiviral agent and/or an agent that enhances cytotoxic efficacy of T lymphocytes.
1. A method for delivering IL-15 superagonist (IL-15SA) to Human Immunodeficiency Virus (HIV)-infected cells, including cells latently infected with HIV, the method comprising
administering, to a subject having or suspected of having an HIV infection, a HIV-specific T cell bound to a nanoparticle that comprises IL-15SA in an amount effective to induce HIV expression from cells latently infected with HIV, wherein the agent is released from the nanoparticle in vivo.
2. The method of claim 1 , further comprising administering to the subject antiretroviral therapy (ART).
3. The method of claim 1 , wherein the HIV-specific T cell is autologous to the subject.
4. The method of claim 1 , wherein the HIV-specific T cell is activated prior to administration to the subject.
5. The method of claim 1 , wherein the HIV-specific T cell is naturally occurring.
6. The method of claim 1 , wherein the HIV-specific T cell is genetically engineered.
7. The method of claim 1 , wherein the nanoparticle is about 20-500 nm in diameter.
8. The method of claim 1 , wherein the HIV-specific T cell is covalently bound to the nanoparticle.
9. The method of claim 1 , wherein the HIV-specific T cell is bound to a plurality of nanoparticles.
10. The method of claim 9 , wherein the HIV-specific T cell is covalently bound to the plurality of nanoparticles.
11. A T pharmacyte comprising a Human Immunodeficiency Virus (HIV)-specific T cell bound to a nanoparticle that comprises IL-15 superagonist (IL-15SA) in an amount effective to induce HIV expression from cells latently infected with HIV.
12. A composition comprising the T pharmacyte of claim 11 .
13. A method comprising contacting a HIV-infected cell with the T pharmacyte of claim 11 , wherein the IL-15SA is released from the nanoparticle.
14. The method of claim 7 , wherein the nanoparticle is about 100-300 nm in diameter.
15. The method of claim 14 , wherein the nanoparticle is about 150 nm in diameter.
16. The method of claim 1 , wherein the nanoparticle is loaded with about 100 μml IL-15SA.
17. The method of claim 9 , wherein the plurality of nanoparticles comprises about 50 to about 100 nanoparticles that each comprise IL-15SA.
18. The method of claim 1 , wherein the nanoparticle is an interbilayer crosslinked multilamellar vesicles (ICMV).
19. A method for delivering IL-15 superagonist (IL-15SA) to Human Immunodeficiency Virus (HIV)-infected cells, the method comprising
administering, to a subject having or suspected of having an HIV infection, a HIV-specific T cell bound to about 50 to about 100 nanoparticles, each nanoparticle comprising about 100 μg/ml IL-15SA, wherein the IL-15SA is released from the nanoparticle in vivo.
20. The method of claim 19 , wherein the nanoparticles are interbilayer crosslinked multilamellar vesicles.