Pitfalls in the use of surrogate markers for human immunodeficiency virus disease: Further evidence on pathogenesis

Allen, Alexandra; Hillis, T. C.; Vidikan, P.; Beer, V.

doi:10.1016/s0306-9877(96)90038-9

Cited by 2 publications

(2 citation statements)

References 10 publications

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“…Cytolin ® is a murine anti-human monoclonal antibody that binds to the S6F1 epitope within LFA-1, preferentially expressed by CD8 + T cells. It has been demonstrated that Cytolin ® administration to HIV-1 infected subjects reduced HIV-1 RNA and increased CD4 T cell count [ 33 , 34 ]. This mAb binds to both HIV-1 virions and CD8+ T cells and dendritic cells.…”

Section: Drugs Targeting the Lymphocyte Function-associated Antigen-1 (Lfa-1)mentioning

confidence: 99%

Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection

Siracusano

Lopalco

2021

Cells

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Since its discovery 35 years ago, there have been no therapeutic interventions shown to enable full HIV-1 remission. Combined antiretroviral therapy (cART) has achieved the sustained control of HIV-1 replication, however, the life-long treatment does not eradicate long-lived latently infected reservoirs and can result in multiple side effects including the development of multidrug-resistant escape mutants. Antibody-based treatments have emerged as alternative approaches for a HIV-1 cure. Here, we will review clinical advances in coreceptor-targeting antibodies, with respect to anti-CCR5 antibodies in particular, which are currently being generated to target the early stages of infection. Among the Env-specific antibodies widely accepted as relevant in cure strategies, the potential role of those targeting CD4-induced (CD4i) epitopes of the CD4-binding site (CD4bs) in eliminating HIV-1 infected cells has gained increasing interest and will be presented. Together, with approaches targeting the HIV-1 replication cycle, we will discuss the strategies aimed at boosting and modulating specific HIV-1 immune responses, highlighting the harnessing of TLR agonists for their dual role as latency reverting agents (LRAs) and immune-modulatory compounds. The synergistic combinations of different approaches have shown promising results to ultimately enable a HIV-1 cure.

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Section: Drugs Targeting the Lymphocyte Function-associated Antigen-1 (Lfa-1)mentioning

confidence: 99%

Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection

Siracusano

Lopalco

2021

Cells

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“…In several small clinical studies [7,8] a reduction in HIV-1 RNA (range 0.2-1 log 10 copies/ml) and a modest increase in CD4 T cell count (range 70–200 cells/mm 3 ) was observed when the antibody was administered to HIV-1 infected individuals. At the time, investigators hypothesized that LFA-1 MAb improved CD4 T cell counts by inhibiting the cytolytic effect of CD8+ T cells (CTL) on activated uninfected CD4+ T cells [7].…”

Section: Introductionmentioning

confidence: 99%

A monoclonal antibody against lymphocyte function-associated antigen-1 decreases HIV-1 replication by inducing the secretion of an antiviral soluble factor

Rychert

Jones

McGrath

et al. 2013

Virol J

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BackgroundLymphocyte Function-Associated Antigen-1 (LFA-1) likely plays a role in the pathogenesis of against HIV-1 and is known to facilitate cell-to-cell transmission of the virus. A monoclonal antibody specific for LFA-1 (Cytolin®) was evaluated as a potential therapeutic in pilot studies performed in the mid-1990s. These uncontrolled human studies suggested that administration of this anti-LFA-1 antibody to HIV-1 infected individuals could provide a modest benefit by decreasing circulating HIV-1 RNA and increasing CD4+ T cell counts. At the time, it was proposed that when bound to cytolytic T cells, the antibody inhibited lysis of activated CD4+ T cells. Given the renewed interest in monoclonal antibody therapy for HIV-1 infected individuals, we investigated possible mechanisms of action of this antibody in vitro.MethodsTo assess whether this anti-LFA-1 antibody binds to HIV-1, a virus capture assay was performed. Binding of the antibody to cells was assessed using flow cytometry. Inhibition of HIV-1 replication was determined in culture by measuring the amount of p24 produced by ELISA. After co-culture of the antibody with peripheral blood mononuclear cells, supernatants were assayed for cytokines and chemokines using various immunoassays.ResultsOur experiments demonstrate that anti-LFA-1 antibody binds to CCR5 and CXCR4 utilizing strains of HIV-1. It also binds to CD8+ T cells and dendritic cells. When bound to virus prior to infection, there is no decrease in HIV-1 replication, suggesting it does not directly inhibit viral replication via virus binding. When bound to cells, it does not inhibit lysis of CD4+ T cells, as was originally hypothesized. Binding to cells does appear to induce the production of a soluble factor that inhibits HIV-1 replication. We determined that this soluble factor was not any of the cytokines or chemokines with known anti-HIV-1 activity. Further, the antibody does not appear to induce any common immune modulating cytokines or chemokines.ConclusionsThese results suggest that one possible mechanism of action of this anti-LFA-1 antibody is to inhibit HIV-1 replication via the production of a soluble antiviral factor that is induced upon binding to cells.

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Pitfalls in the use of surrogate markers for human immunodeficiency virus disease: Further evidence on pathogenesis

Cited by 2 publications

References 10 publications

Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection

Immunotherapy with Cell-Based Biological Drugs to Cure HIV-1 Infection

A monoclonal antibody against lymphocyte function-associated antigen-1 decreases HIV-1 replication by inducing the secretion of an antiviral soluble factor

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