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 method of treating an individual that carries latent human immunodeficiency virus (HIV) infected cells, the method comprising:
administering to the individual ALT-803, and a broadly neutralizing anti-HIV antibody (bNAb).
2. The method of claim 1 , wherein the bNAb is selected from the group consisting of PGT121, 10-1074, 10E8, 10E8v4-V5R-100cF, 2F5, 2G12, 3BNC117, CAP256.VRC26.25, N6, PG9, PGDM1400, VRC01, and VRC07-523.
3. The method of claim 2 , further comprising administering a histone deacetylase (HDAC) inhibitor.
4. The method of claim 3 , wherein the HDAC inhibitor is vorinostat, panobinostat, valproic acid, phenylbutyrate, entinostat, CI-994, mocetinostat, Viracta 3996, dacinostat, pivanex, givinostat, or belinostat.
5. The method of claim 4 , wherein the HDAC inhibitor is administered at least 24 hours before or after the ALT-803.
6. The method of claim 5 , wherein a natural killer cell that is genetically modified to express a high affinity CD16 receptor is also administered to the individual.
7. The method of claim 5 , wherein a vaccine composition is also administered to the individual, and wherein the vaccine composition is a bacterial vaccine, a yeast vaccine, or a viral vaccine, and further wherein the vaccine composition comprises a recombinant nucleic acid that encodes at least one HIV antigen.
8. The method of claim 7 , wherein the bacterial vaccine is an Escherichia coli vaccine that is genetically engineered to have reduced or lacking expression of lipopolysaccharide.
9. The method of claim 7 , wherein the yeast vaccine is a Saccharomyces cerevisiae vaccine.
10. The method of claim 7 , wherein the viral vaccine is an adenoviral vaccine.
11. The method of claim 6 , wherein the natural killer cell is an autologous NK cell, an NK92 cell, an aNK cell, a haNK cell, or a taNK cell.
12. The method of claim 5 , further comprising administering a CAR-T cell that has a chimeric antigen receptor (CAR) with an ectodomain that binds to CD2, CD20, or CD32.
13. The method of claim 7 , wherein the individual is administered two or more of the vaccine compositions.
14. The method of claim 8 , wherein the individual is administered three or more of the vaccine compositions.
15. The method of claim 7 , wherein a natural killer cell that is genetically modified to express a high affinity CD16 receptor is also administered to the individual.