Targeting reservoirs of HIV replication in lymphoid follicles with cellular therapies to cure HIV

Skinner, Pamela J.

doi:10.1002/acg2.27

Cited by 4 publications

(3 citation statements)

References 89 publications

(109 reference statements)

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“…To achieve better long-term control of infection, CAR/CXCR5-T cell immunotherapy could also be combined with other strategies aimed at eliminating the HIV/SIV reservoir. Such therapies might include latency reversal agents [62,97] or agents that modify the immune system [98], such as an IL-15 superagonist [99].…”

Section: Plos Pathogensmentioning

confidence: 99%

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CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection

et al. 2022

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During chronic human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection prior to AIDS progression, the vast majority of viral replication is concentrated within B cell follicles of secondary lymphoid tissues. We investigated whether infusion of T cells expressing an SIV-specific chimeric antigen receptor (CAR) and the follicular homing receptor, CXCR5, could successfully kill viral-RNA+ cells in targeted lymphoid follicles in SIV-infected rhesus macaques. In this study, CD4 and CD8 T cells from rhesus macaques were genetically modified to express antiviral CAR and CXCR5 moieties (generating CAR/CXCR5-T cells) and autologously infused into a chronically infected animal. At 2 days post-treatment, the CAR/CXCR5-T cells were located primarily in spleen and lymph nodes both inside and outside of lymphoid follicles. Few CAR/CXCR5-T cells were detected in the ileum, rectum, and lung, and no cells were detected in the bone marrow, liver, or brain. Within follicles, CAR/CXCR5-T cells were found in direct contact with SIV-viral RNA+ cells. We next infused CAR/CXCR5-T cells into ART-suppressed SIV-infected rhesus macaques, in which the animals were released from ART at the time of infusion. These CAR/CXCR5-T cells replicated in vivo within both the extrafollicular and follicular regions of lymph nodes and accumulated within lymphoid follicles. CAR/CXR5-T cell concentrations in follicles peaked during the first week post-infusion but declined to undetectable levels after 2 to 4 weeks. Overall, CAR/CXCR5-T cell-treated animals maintained lower viral loads and follicular viral RNA levels than untreated control animals, and no outstanding adverse reactions were noted. These findings indicate that CAR/CXCR5-T cell treatment is safe and holds promise as a future treatment for the durable remission of HIV.

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Section: Plos Pathogensmentioning

confidence: 99%

“…We hypothesize that increasing the numbers of HIV-specific CD8 + T cells in B cell follicles will decrease viral replication within the follicles and lead to durable control of HIV [62,63]. In this study, we tested this hypothesis in an SIV-infected rhesus macaque model of HIV infection.…”

Section: Introductionmentioning

confidence: 99%

CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection

et al. 2022

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“…To achieve better long-term control of infection, CAR/CXCR5-T cell immunotherapy could also be combined with other strategies aimed at eliminating the HIV/SIV reservoir. Such therapies might include latency reversal agents 62,95 or agents that modify the immune system 96 , such as an IL-15 superagonist 97 .…”

Section: Discussionmentioning

confidence: 99%

CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection

Pampusch

Abdelaal

Cartwright

et al. 2021

Preprint

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During chronic human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection prior to AIDS progression, the vast majority of viral replication is concentrated within B cell follicles of secondary lymphoid tissues. We investigated whether infusion of T cells expressing an SIV-specific chimeric antigen receptor (CAR) and the follicular homing receptor, CXCR5, could successfully kill viral-RNA + cells in targeted lymphoid follicles in SIV-infected rhesus macaques. In this study, CD4 and CD8 T cells from rhesus macaques were genetically modified to express antiviral CAR and CXCR5 moieties (generating CAR/CXCR5-T cells) and autologously infused into a chronically infected animal. At 2 days post-treatment, the CAR/CXCR5-T cells were located primarily in spleen and lymph nodes both inside and outside of lymphoid follicles. Few CAR/CXCR5-T cells were detected in the rectum and lung, and no cells were detected in the bone marrow, liver, brain, or ileum. Within follicles, CAR/CXCR5-T cells were found in direct contact with SIV viral RNA+ cells. We next infused CAR/CXCR5-T cells into ART-suppressed SIV-infected rhesus macaques, in which the animals were released from ART at the time of infusion. These CAR/CXCR5-T cells replicated in vivo within both the extrafollicular and follicular regions of lymph nodes and accumulated within lymphoid follicles. CAR/CXR5-T cell concentrations in follicles peaked during the first week post-infusion but declined to undetectable levels after 2 to 4 weeks. Overall, CAR/CXCR5-T cell-treated animals maintained lower viral loads and follicular viral RNA levels than untreated control animals, and no outstanding adverse reactions were noted. These findings indicate that CAR/CXCR5-T cell treatment is safe and holds promise as a future treatment for the durable remission of HIV.

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Could gene therapy cure HIV?

et al. 2021

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Targeting reservoirs of HIV replication in lymphoid follicles with cellular therapies to cure HIV

Cited by 4 publications

References 89 publications

CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection

CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection

CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection

Could gene therapy cure HIV?

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