Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120 human IgG1κ monoclonal antibody, in HIV-1 infected cells

Clayton, R. M.; Öhagen, Åsa; Goethals, Olivia; Smets, Alexandra; Loock, Marnix Van; Michiels, Lieve; Kennedy-Johnston, Erin; Cunningham, Mark; Jiang, Haiyan; Bola, Sharon; Gutshall, Lester L.; Gunn, George R.; Vecchio, Alfred Del; Sarisky, Robert T.; Hallenberger, Sabine; Hertogs, Kurt

doi:10.1016/j.jviromet.2006.08.017

Cited by 9 publications

(6 citation statements)

References 15 publications

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“…F105 bound exclusively to cells expressing gp120 in a co receptor-independent manner and did not bind to HIV-uninfected cells. These data further support the potential of mAbs as immunotherapeutic targeting agents and offer new insights into the possibility of F105 as an excellent targeting moiety for the selective delivery of antiretroviral drugs or cytotoxic compounds to HIV-1-infected cells [127].…”

Section: Immunotherapy For Hiv Infection Reviewsupporting

confidence: 63%

Immunotherapeutic Restoration in HIV-Infected Individuals

Kim¹,

Han

2011

Immunotherapy

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While the development of combined active antiretroviral therapy (cART) has dramatically improved life expectancies and quality of life in HIV-infected individuals, long-term clinical problems, such as metabolic complications, remain important constraints of life-long cART. Complete immune restoration using only cART is normally unattainable even in cases of sufficient plasma viral suppression. The need for immunologic adjuncts that complement cART remains, because while cART alone may result in the complete recovery of peripheral net CD4+ T lymphocytes, it may not affect the reservoir of HIV-infected cells. Here, we review current immunotherapies for HIV infection, with a particular emphasis on recent advances in cytokine therapies, therapeutic immunization, monoclonal antibodies, immune-modulating drugs, nanotechnology-based approaches and radioimmunotherapy.

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Section: Immunotherapy For Hiv Infection Reviewsupporting

confidence: 63%

Immunotherapeutic Restoration in HIV-Infected Individuals

Kim¹,

Han

2011

Immunotherapy

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“…Furthermore, sCD4 has been reported to bind to envelope proteins, including IIIB gp120, with K D values of 22 to 35 nM (12,59,88). Another study reported K D values in the range of 2.2 to 16 nM for a range of anti-CD4bs Fab fragments (including Fab b12) to MN gp120 (62).…”

Section: Fig 2 Vhh and Mab B12 Icmentioning

confidence: 99%

“…Another study reported K D values in the range of 2.2 to 16 nM for a range of anti-CD4bs Fab fragments (including Fab b12) to MN gp120 (62). Another human anti-CD4bs MAb, F105, has been shown to bind to IIIB gp120 with a K D of 0.62 nM (12).…”

Section: Fig 2 Vhh and Mab B12 Icmentioning

confidence: 99%

Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120

Forsman

Beirnaert

Aasa-Chapman

et al. 2008

J Virol

111

138

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Members of the Camelidae family produce immunoglobulins devoid of light chains. We have characterized variable domains of these heavy chain antibodies, the VHH, from llamas immunized with human immunodeficiency virus type 1 (HIV-1) envelope protein gp120 in order to identify VHH that can inhibit HIV-1 infection. To increase the chances of isolating neutralizing VHH, we employed a functional selection approach, involving panning of phage libraries expressing the VHH repertoire on recombinant gp120, followed by a competitive elution with soluble CD4. By immunizing with gp120 derived from an HIV-1 subtype B /C primary isolate, followed by panning on gp120 from HIV-1 isolates of subtypes A, B, and C, we could select for VHH with cross-subtype neutralizing activity. Three VHH able to neutralize HIV-1 primary isolates of subtypes B and C were characterized. These bound to recombinant gp120 with affinities close to the suggested affinity ceiling for in vivo-maturated antibodies and competed with soluble CD4 for this binding, indicating that their mechanism of neutralization involves interacting with the functional envelope spike prior to binding to CD4. The most potent VHH in terms of low 50% inhibitory concentration (IC 50 ) and IC 90 values and cross-subtype reactivity was A12. These results indicate that camelid VHH can be potent HIV-1 entry inhibitors. Since VHH are stable and can be produced at a relatively low cost, they may be considered for applications such as HIV-1 microbicide development. Antienvelope VHH might also prove useful in defining neutralizing and nonneutralizing epitopes on HIV-1 envelope proteins, with implications for HIV-1 vaccine design.

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“…F105 displays higher affinity to gp120 even at nanomolar concentrations. Crystal structure analysis of the binding fragment of F105 reveals a H-loop containing a unique sequence of serine and tyrosine residues and a phenyl alanine residue at the apex [19]. It is proposed that this phenyl alanine residue in F105 associates with the binding pocket of gp120 similar to the phenyl alanine residue (Phe43) from CD4 of the host cells.…”

Section: Glycoprotein-120 (Gp120)mentioning

confidence: 99%

“…The bi-specific antibody reported against HIV infected cells was found to bind specifically with the gp120 fragment exposed in the infected cells as well as to the C3d, a component of the complement resulting in the activation of the complement-mediated lysis of the infected cells. A broad activity antibody against gp120, F105 has also been used to target the HIV infected cells [19]. F105 displays higher affinity to gp120 even at nanomolar concentrations.…”

Section: Glycoprotein-120 (Gp120)mentioning

confidence: 99%

Targeting strategies for delivery of anti-HIV drugs

Ramana

Anand

Sethuraman

et al. 2014

Journal of Controlled Release

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Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS-related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug-drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti-HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti-retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body.

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Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120 human IgG1κ monoclonal antibody, in HIV-1 infected cells

Cited by 9 publications

References 15 publications

Immunotherapeutic Restoration in HIV-Infected Individuals

Immunotherapeutic Restoration in HIV-Infected Individuals

Llama Antibody Fragments with Cross-Subtype Human Immunodeficiency Virus Type 1 (HIV-1)-Neutralizing Properties and High Affinity for HIV-1 gp120

Targeting strategies for delivery of anti-HIV drugs

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