Bispecific antibodies: Potential immunotherapies for HIV treatment

Fabozzi, Giulia; Pegu, Amarendra; Koup, Richard A.; Petrovas, Constantinos

doi:10.1016/j.ymeth.2018.10.010

Cited by 19 publications

(15 citation statements)

References 95 publications

(103 reference statements)

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“…showed that this bispecific antibody bound to EBOV is internalized into endo-lysosomal compartments where it potently blocks Ebola interaction with its intracellular receptor 28 . This strategy, already tested for HIV 29 , has been shown to protect mice, even when administered 2 days after challenge with EBOV 28 .…”

Section: Inhibition Of Receptor Bindingmentioning

confidence: 99%

Targeting viral entry as a strategy for broad-spectrum antivirals

Mazzon

Marsh

2019

F1000Res

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The process of entry into a host cell is a key step in the life cycle of most viruses. In recent years, there has been a significant increase in our understanding of the routes and mechanisms of entry for a number of these viruses. This has led to the development of novel broad-spectrum antiviral approaches that target host cell proteins and pathways, in addition to strategies focused on individual viruses or virus families. Here we consider a number of these approaches and their broad-spectrum potential.

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Section: Inhibition Of Receptor Bindingmentioning

confidence: 99%

Targeting viral entry as a strategy for broad-spectrum antivirals

Mazzon

Marsh

2019

F1000Res

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“…Antibody-based target cell killing has been advanced in cancer treatment and is moving to the forefront of therapeutic approaches against diverse viral pathogens, including HIV-1. Specific efforts include adoptive transfer of T cells, e.g., natural virus-specific T cells expanded ex vivo [ 35 ] or genetically modified T cells expressing cloned T-cell receptors or chimeric antigen receptors [ 36 , 37 ]; another T-cell-mediated technology involves bispecific T-cell-engaging antibodies [ 38 ]. Distinct from these technically complex cell-mediated strategies, RIT technology typically involves intravenous infusion of a purified protein for direct killing of infected cells [ 39 , 40 ]; RITs targeting HIV-1 and other specific viral pathogens have been described [ 41 – 43 ].…”

Section: Discussionmentioning

confidence: 99%

An immunotoxin targeting Ebola virus glycoprotein inhibits Ebola virus production from infected cells

et al. 2021

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Ebola virus (EBOV), a member of the mononegaviral family Filoviridae, causes severe disease associated with high lethality in humans. Despite enormous progress in development of EBOV medical countermeasures, no anti-EBOV treatment has been approved. We designed an immunotoxin in which a single-chain variable region fragment of the EBOV glycoprotein-specific monoclonal antibody 6D8 was fused to the effector domains of Pseudomonas aeruginosa exotoxin A (PE38). This immunotoxin, 6D8-PE38, bound specifically to cells expressing EBOV glycoproteins. Importantly, 6D8-PE38 targeted EBOV-infected cells, as evidenced by inhibition of infectious EBOV production from infected cells, including primary human macrophages. The data presented here provide a proof of concept for immunotoxin-based targeted killing of infected cells as a potential antiviral intervention for Ebola virus disease.

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“…This approach for more individualized treatment in future applications is a logical choice for treatment such as targeting host proteins or engineered multi-targeting antibodies become more available. The requirement for cocktails of bNAbs has long been realized, but new ideas for combination therapy include using specifically engineered antibody molecules with the capability to target multiple epitopes (127)(128)(129)(130), such as bi-specific antibodies (bsAbs) (131)(132)(133), with the 10E8.4/iMab now in clinical trials. Bispecific T-cell engagers (BiTEs) have been developed so far primarily for oncology (134)(135)(136), but now also for HIV therapeutics (137).…”

Section: Isotype and Multi-epitope Targetingmentioning

confidence: 99%

Advancing HIV Broadly Neutralizing Antibodies: From Discovery to the Clinic

Spencer

Shapiro

Haigwood

et al. 2021

Front. Public Health

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Despite substantial progress in confronting the global HIV-1 epidemic since its inception in the 1980s, better approaches for both treatment and prevention will be necessary to end the epidemic and remain a top public health priority. Antiretroviral therapy (ART) has been effective in extending lives, but at a cost of lifelong adherence to treatment. Broadly neutralizing antibodies (bNAbs) are directed to conserved regions of the HIV-1 envelope glycoprotein trimer (Env) and can block infection if present at the time of viral exposure. The therapeutic application of bNAbs holds great promise, and progress is being made toward their development for widespread clinical use. Compared to the current standard of care of small molecule-based ART, bNAbs offer: (1) reduced toxicity; (2) the advantages of extended half-lives that would bypass daily dosing requirements; and (3) the potential to incorporate a wider immune response through Fc signaling. Recent advances in discovery technology can enable system-wide mining of the immunoglobulin repertoire and will continue to accelerate isolation of next generation potent bNAbs. Passive transfer studies in pre-clinical models and clinical trials have demonstrated the utility of bNAbs in blocking or limiting transmission and achieving viral suppression. These studies have helped to define the window of opportunity for optimal intervention to achieve viral clearance, either using bNAbs alone or in combination with ART. None of these advances with bNAbs would be possible without technological advancements and expanding the cohorts of donor participation. Together these elements fueled the remarkable growth in bNAb development. Here, we review the development of bNAbs as therapies for HIV-1, exploring advances in discovery, insights from animal models and early clinical trials, and innovations to optimize their clinical potential through efforts to extend half-life, maximize the contribution of Fc effector functions, preclude escape through multiepitope targeting, and the potential for sustained delivery.

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Bispecific antibodies: Potential immunotherapies for HIV treatment

Cited by 19 publications

References 95 publications

Targeting viral entry as a strategy for broad-spectrum antivirals

Targeting viral entry as a strategy for broad-spectrum antivirals

An immunotoxin targeting Ebola virus glycoprotein inhibits Ebola virus production from infected cells

Advancing HIV Broadly Neutralizing Antibodies: From Discovery to the Clinic

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