Treatment of immunosuppressed subjects
An EL-15 super agonist (IL-15N72D:IL-15RαSU/IgG1Fc; N-803) increases circulating NK cells, effector memory and effector memory RA cells in post-allogeneic hematopoietic stem cell transplant patients (HCT). Methods of treatment include administration of N-803 to subjects in need of such treatment.
1. A method of treating a subject suffering from a human immunodeficiency virus (HIV) latent infection comprising culturing immune effector cells, stem cells, or combinations thereof, ex vivo with an effective amount of an IL-15:IL-15Rα complex and adoptively transferring the cultured cells to the subject, wherein the IL-15:IL-15Rα complex in the cultured cells is administered to the subject in escalating therapeutically effective amounts over a period of time to maintain an HIV specific immune response, wherein the effective amounts are from about 1 mcg/kg up to 6.0 mcg/kg and wherein the effective amounts are administered in three separate doses with an escalation of the effective amount per dose, and wherein the IL-15:IL-15Rα complex is an IL-15N72D:IL-15RαSu/Fc complex (N-803) comprising a dimeric IL-15RαSu/Fc and two IL-15N72D molecules and modulates amounts of circulating immune effector cells and/or activates immune effector cells.
2. The method of claim 1 , wherein the IL-15:IL-15Rα complex is administered until the HIV is undetectable or eradicated from the subject.
3. The method of claim 1 , wherein the immune effector cells comprise natural killer cells (NK), cytolytic CD8 + T cells (CTLs), CD4 + T helper cells (T H ), effector memory (T EM ) T cells (CD45RA − /CCR7 − ), effector memory RA (T EMRA ) T cells (CD45RA + /CCR7 − ), or combinations thereof.
4. The method of claim 1 , further comprising administering one or more chemotherapeutic agents, compounds, cytokine antagonist, cytokine receptor antagonist, cytokines, adoptive cell therapy, anti-viral agents, checkpoint inhibitors, adjuvants or combinations thereof.
5. The method of claim 4 , wherein the anti-viral agent comprises: a non-nucleoside reverse transcriptase inhibitor (NNRTI) selected from the group consisting of etravirine, efavirenz, nevirapine, rilpivirine, delavirdine, and combinations thereof; a nucleoside reverse transcriptase inhibitor (NRTI) selected from the group consisting of lamivudine, zidovudine, emtricitabine, abacavir, zalcitabine, dideoxycytidine, azidothymidine, tenofovir disoproxil fumarate, didanosine (ddI EC), dideoxyinosine, stavudine, abacavir sulfate, and combinations thereof a protease inhibitor selected from the group consisting of amprenavir, tipranavir, indinavir, saquinavir mesylate, lopinavir and ritonavir (LPV/RTV), Fosamprenavir Calcium (FOS-APV), ritonavir, darunavir, atazanavir sulfate, nelfinavir mesylate, and combinations thereof or combinations thereof.
6. The method of claim 1 , wherein the immune effector cells, stem cells, or combinations thereof comprise: allogeneic, autologous, syngeneic, related, unrelated, HLA-matched, HLA-mismatched or haploidentical cells.