Safety and Virologic Impact of Haploidentical NK Cells Plus Interleukin 2 or N-803 in HIV Infection

Natural killer (NK) cells are dysfunctional in chronic human immunodeficiency virus (HIV) infection as they are not able to clear virus. We hypothesized that an infusion of NK cells, supported by interleukin 2 (IL-2) or IL-15, could decrease virus-producing cells in the lymphatic tissues. We conduct...

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Published in:The Journal of infectious diseases 2024-05, Vol.229 (5), p.1256-1265
Main Authors: Miller, Jeffrey S, Rhein, Joshua, Davis, Zachary B, Cooley, Sarah, McKenna, David, Anderson, Jodi, Escandón, Kevin, Wieking, Garritt, Reichel, Jarrett, Thorkelson, Ann, Jorstad, Siri, Safrit, Jeffrey T, Soon-Shiong, Patrick, Beilman, Gregory J, Chipman, Jeffrey G, Schacker, Timothy W
Format: Article
Language:English
Subjects:
Adult
Female
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
Humans
Interleukin-15
Interleukin-2
Killer Cells, Natural - immunology
Lymph Nodes - immunology
Male
Middle Aged
Pilot Projects
Viral Load
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Summary:Natural killer (NK) cells are dysfunctional in chronic human immunodeficiency virus (HIV) infection as they are not able to clear virus. We hypothesized that an infusion of NK cells, supported by interleukin 2 (IL-2) or IL-15, could decrease virus-producing cells in the lymphatic tissues. We conducted a phase 1 pilot study in 6 persons with HIV (PWH), where a single infusion of haploidentical related donor NK cells was given plus either IL-2 or N-803 (an IL-15 superagonist). The approach was well tolerated with no unexpected adverse events. We did not pretreat recipients with cyclophosphamide or fludarabine to "make immunologic space," reasoning that PWH on stable antiretroviral treatment remain T-cell depleted in lymphatic tissues. We found donor cells remained detectable in blood for up to 8 days (similar to what is seen in cancer pretreatment with lymphodepleting chemotherapy) and in the lymph nodes and rectum up to 28 days. There was a moderate decrease in the frequency of viral RNA-positive cells in lymph nodes. There was a moderate decrease in HIV-producing cells in lymph nodes. Further studies are warranted to determine the impact of healthy NK cells on HIV reservoirs and if restoring NK-cell function could be part of an HIV cure strategy. Clinical Trials Registration. NCT03346499 and NCT03899480.
ISSN:0022-1899
1537-6613
1537-6613
DOI:10.1093/infdis/jiad578