Lack of Specific Regulatory T Cell Depletion and Cytoreduction Associated with Extensive Toxicity After Administration of Low and High Doses of Cyclophosphamide

Kleinman, Adam J.; Sivanandham, Ranjit; Sette, Paola; Brocca-Cofano, Egidio; McAndrews, Colin; Keele, Brandon F.; Pandrea, Ivona; Apetrei, Cristian

doi:10.1089/aid.2021.0036

Cited by 2 publications

(6 citation statements)

References 15 publications

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“…However, in SIVsab-infected RMs, low dose Cy did not result in acceptable Treg specificity, nor did it greatly induce T-cell activation nor viral reactivation [593]. With additional toxicity occurring when Cy is combined with ART [593], Treg depletion via Cy loses feasibility.…”

Section: Cyclophosphamide (Cy) For Treg Depletionmentioning

confidence: 98%

“…In persons treated with low dose metronomic Cy for four total weeks, Treg depletion occurred and resulted in bolstered cell-mediated cytotoxicity [592]. However, in SIVsab-infected RMs, low dose Cy did not result in acceptable Treg specificity, nor did it greatly induce T-cell activation nor viral reactivation [593]. With additional toxicity occurring when Cy is combined with ART [593], Treg depletion via Cy loses feasibility.…”

Section: Cyclophosphamide (Cy) For Treg Depletionmentioning

confidence: 99%

“…For example, the use of IL2-DT for Treg depletion had a positive impact on the spontaneously functionally cured SIV infection in RMs [441], but when combined with ART, resulted in unacceptable toxicity [442]. Similarly, Cy used as a cytoreductive agent close to chemotherapeutic dosage with ART resulted in unacceptable toxicity and morbidity [593]. Further, the venetoclax + ixazomib combination had synergistic in vitro efficacy, but did not make it to in vivo testing because ex vivo toxicity with PBMCs was too great [485].…”

Section: Crosstalk Between Macrophages and Exhausted T Cellsmentioning

confidence: 99%

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So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research

Kleinman

Pandrea

Apetrei

2022

Viruses

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HIV infection requires lifelong antiretroviral therapy (ART) to control disease progression. Although ART has greatly extended the life expectancy of persons living with HIV (PWH), PWH nonetheless suffer from an increase in AIDS-related and non-AIDS related comorbidities resulting from HIV pathogenesis. Thus, an HIV cure is imperative to improve the quality of life of PWH. In this review, we discuss the origins of various SIV strains utilized in cure and comorbidity research as well as their respective animal species used. We briefly detail the life cycle of HIV and describe the pathogenesis of HIV/SIV and the integral role of chronic immune activation and inflammation on disease progression and comorbidities, with comparisons between pathogenic infections and nonpathogenic infections that occur in natural hosts of SIVs. We further discuss the various HIV cure strategies being explored with an emphasis on immunological therapies and “shock and kill”.

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Section: Cyclophosphamide (Cy) For Treg Depletionmentioning

confidence: 98%

Section: Cyclophosphamide (Cy) For Treg Depletionmentioning

confidence: 99%

Section: Crosstalk Between Macrophages and Exhausted T Cellsmentioning

confidence: 99%

See 1 more Smart Citation

So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research

Kleinman

Pandrea

Apetrei

2022

Viruses

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“…Low and high doses of Cy were administered to SIV-infected RMs to assess their effects on the SIV reservoirs. As a Treg-depleting agent, Cy unselectively depleted Treg and total lymphocytes, resulting in minimal immune activation and no viral reactivation [ 379 ]. As a cytoreductive agent, Cy induced massive viral reactivation in EC RMs without ART [ 379 ].…”

Section: Experimental Dissection Of Immune Responses In Siv Infectionmentioning

confidence: 99%

“…As a Treg-depleting agent, Cy unselectively depleted Treg and total lymphocytes, resulting in minimal immune activation and no viral reactivation [ 379 ]. As a cytoreductive agent, Cy induced massive viral reactivation in EC RMs without ART [ 379 ]. However, when administered with ART, Cy had substantial adverse effects, including mortality [ 379 ].…”

Section: Experimental Dissection Of Immune Responses In Siv Infectionmentioning

confidence: 99%

Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

Symmonds,

Gaufin,

et al. 2024

Viruses

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Understanding the underlying mechanisms of HIV pathogenesis is critical for designing successful HIV vaccines and cure strategies. However, achieving this goal is complicated by the virus’s direct interactions with immune cells, the induction of persistent reservoirs in the immune system cells, and multiple strategies developed by the virus for immune evasion. Meanwhile, HIV and SIV infections induce a pandysfunction of the immune cell populations, making it difficult to untangle the various concurrent mechanisms of HIV pathogenesis. Over the years, one of the most successful approaches for dissecting the immune correlates of protection in HIV/SIV infection has been the in vivo depletion of various immune cell populations and assessment of the impact of these depletions on the outcome of infection in non-human primate models. Here, we present a detailed analysis of the strategies and results of manipulating SIV pathogenesis through in vivo depletions of key immune cells populations. Although each of these methods has its limitations, they have all contributed to our understanding of key pathogenic pathways in HIV/SIV infection.

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Lack of Specific Regulatory T Cell Depletion and Cytoreduction Associated with Extensive Toxicity After Administration of Low and High Doses of Cyclophosphamide

Cited by 2 publications

References 15 publications

So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research

So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research

Making a Monkey out of Human Immunodeficiency Virus/Simian Immunodeficiency Virus Pathogenesis: Immune Cell Depletion Experiments as a Tool to Understand the Immune Correlates of Protection and Pathogenicity in HIV Infection

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