HIV treatment compositions and methods
HIV treatment, and especially treatment of latent infected CD4 cells, can be significantly improved using a kick-and-kill approach that employs an immune stimulation component and/or HDAC inhibition as one treatment component, and that may also include a second component in which a vaccine composition, various NK cells, CAR-T cells, and/or broadly neutralizing antibodies are administered.
1. A treatment kit for use in reducing a latent viral reservoir in an HIV infected individual, the kit comprising ALT-803 and a histone deacetylase (HDAC) inhibitor;
wherein the ALT-803 and the HDAC inhibitor are present in sufficient quantity to trigger, upon administration to the individual, expression of viral antigens in the HIV infected cell.
2. The treatment kit of claim 1 further comprising one additional component selected form the group consisting of (a) a vaccine composition that generates an immune response against the viral antigen, (b) a natural killer cell that is optionally genetically modified to express a high affinity CD16 receptor or a chimeric antigen receptor, (c) a CAR-T cell, and (d) a broadly neutralizing antibody or antigen binding fragment thereof.
3. The treatment kit of claim 1 further comprising two additional components selected form the group consisting of (a) a vaccine composition that generates an immune response against the viral antigen, (b) a natural killer cell that is optionally genetically modified to express a high affinity CD16 receptor or a chimeric antigen receptor, (c) a CAR-T cell, and (d) a broadly neutralizing antibody or antigen binding fragment thereof.
4. The treatment kit of claim 1 further comprising three additional components selected form the group consisting of (a) a vaccine composition that generates an immune response against the viral antigen, (b) a natural killer cell that is optionally genetically modified to express a high affinity CD16 receptor or a chimeric antigen receptor, (c) a CAR-T cell, and (d) a broadly neutralizing antibody or antigen binding fragment thereof.
5. The treatment kit of claim 1 further comprising (a) a vaccine composition that generates an immune response against the viral antigen, (b) a natural killer cell that is optionally genetically modified to express a high affinity CD16 receptor or a chimeric antigen receptor, (c) a CAR-T cell, and (d) a broadly neutralizing antibody or antigen binding fragment thereof.
6. The treatment kit of claim 1 , wherein the ALT-803 further comprises a binding portion that binds to the viral antigen or an antigen on a CD4 T cell, and wherein the antigen on the CD4 T cell is CD2, CD20, or CD32.
7. The treatment kit of claim 1 , wherein the HDAC inhibitor is vorinostat, panobinostat, valproic acid, phenylbutyrate, entinostat, CI-994, mocetinostat, Viracta 3996, dacinostat, pivanex, givinostat, or belinostat.
8. The treatment kit of claim 2 , wherein the (a) vaccine composition that generates an immune response against the viral antigen, (b) natural killer cell that is optionally genetically modified to express a high affinity CD16 receptor or a chimeric antigen receptor, (c) CAR-T cell, and/or (d) broadly neutralizing antibody or antigen binding fragment thereof are formulated to allow for separate administration from administration of the ALT-803 and the HDAC inhibitor.
9. The treatment kit of claim 2 , wherein the vaccine composition is a bacterial vaccine, a yeast vaccine, or a viral vaccine, and wherein the vaccine composition comprises a recombinant nucleic acid that encodes at least one viral antigen of the HIV.
10. The treatment kit of claim 9 , wherein the bacterial vaccine is an E. coli vaccine that is genetically engineered to have reduced or lacking expression of lipopolysaccharide.
11. The treatment kit of claim 9 , wherein the yeast vaccine is an S. cerevisiae vaccine.
12. The treatment kit of claim 9 , wherein the viral vaccine is an adenoviral vaccine.
13. The treatment kit of claim 2 , wherein the natural killer cell is an autologous NK cell, an NK92 cell, an aNK cell, a haNK cell, or a taNK cell.
14. The treatment kit of claim 2 , wherein the CAR-T cell has a chimeric antigen receptor with an ectodomain that binds to CD2, CD20, or CD32.
15. The treatment kit of claim 2 , wherein the broadly neutralizing antibody binds to a gp41 interface site of gp120, a V1/V2-glycan site of gp120, a V3-glycan site of gp120, or a CD4 binding site of gp120, or wherein the broadly neutralizing antibody is selected from the group consisting of PGT121, 10-1074,10E8,10E8v4-V5R-100cF, 2F5, 2G12, 3BNC117, CAP256.VRC26.25, N6, PG9, PGDM1400, PGT121, VRC01, and VRC07-523.
16. The treatment kit of claim 1 , wherein the ALT-803 is formulated for intravenous and/or subcutaneous injection.
17. The treatment kit of claim 1 , wherein the HDAC inhibitor is formulated for oral administration.
18. The treatment kit of claim 1 , wherein the natural killer cell has an antibody bound to the natural killer cell, wherein the antibody specifically or preferentially binds to latent HIV infected cells.
19. The treatment kit of claim 1 , wherein administration of the ALT-803 and the HDAC inhibitor is contemporaneous.
20. The treatment kit of claim 1 , wherein administration of the ALT-803 and the HDAC inhibitor is separated from administration of the (a) vaccine composition that generates an immune response against the viral antigen, (b) natural killer cell that is optionally genetically modified to express a high affinity CD16 receptor or a chimeric antigen receptor, (c) CAR-T cell, and/or (d) broadly neutralizing antibody or antigen binding fragment thereof by at least 24 hours.