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Review
. 2023 Jul 1;18(4):184-190.
doi: 10.1097/COH.0000000000000796. Epub 2023 May 4.

Engineering strategies of Anti-HIV antibody therapeutics in clinical development

Nicole Pihlstrom  1 , Stylianos Bournazos
Affiliations
Review

Engineering strategies of Anti-HIV antibody therapeutics in clinical development

Nicole Pihlstrom et al. Curr Opin HIV AIDS. .

Abstract

Purpose of review: Anti-human immunodeficiency virus (HIV) antibody-based therapeutics offer an alternative treatment option to current antiretroviral drugs. This review aims to provide an overview of the Fc- and Fab-engineering strategies that have been developed to optimize broadly neutralizing antibodies and discuss recent findings from preclinical and clinical studies.

Recent findings: Multispecific antibodies, including bispecific and trispecific antibodies, DART molecules, and BiTEs, as well as Fc-optimized antibodies, have emerged as promising therapeutic candidates for the treatment of HIV. These engineered antibodies engage multiple epitopes on the HIV envelope protein and human receptors, resulting in increased potency and breadth of activity. Additionally, Fc-enhanced antibodies have demonstrated extended half-life and improved effector function.

Summary: The development of Fc and Fab-engineered antibodies for the treatment of HIV continues to show promising progress. These novel therapies have the potential to overcome the limitations of current antiretroviral pharmacologic agents by more effectively suppressing viral load and targeting latent reservoirs in individuals living with HIV. Further studies are needed to fully understand the safety and efficacy of these therapies, but the growing body of evidence supports their potential as a new class of therapeutics for the treatment of HIV.

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Conflict of interest statement

Conflicts of interest: None.

Figures

Figure 1.
Figure 1.. Structures of multispecific, Fab engineered antibodies to improve breadth and potency.
These antibodies demonstrate the diversity of forms and engineering methods that allow for the simultaneous targeting of multiple epitopes on the Env and/or human cellular receptors. Antigen binding is facilitated via the Fab region while effector function engagement is mediated via the Fc as shown in (A). The structures represent (A) non-engineered IgG, (B) bispecific antibody, (C) hinge-domain engineered antibody, (D) trispecific antibody, (E) DART molecule with and without a Fc, and (F) BiTEs.
Figure 2.
Figure 2.. Diversity of effector functions mediated by IgG antibodies.
IgG Fab domain binds to the Env presented on HIV infected cells or virions thereby recruiting effector cell functions through the engagement of FcγRs by the IgG Fc domain. These pleiotropic effector functions are the outcome of the engagement of specific FcγRs on B cells, natural killer (NK) cells, dendritic cells (DC), granulocytes, monocytes, and macrophages.
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References

    1. Cuevas JM GR, Garijo R, López-Aldeguer J, Sanjuán R. Extremely High Mutation Rate of HIV-1 In Vivo. PLoS Biol. Sep 6 2015;13(9):e1002251. - PMC - PubMed
    1. Udeze AO OD, Odaibo GN. Polymorphisms and drug resistance analysis of HIV-1 isolates from patients on first line antiretroviral therapy (ART) in South-eastern Nigeria. PLoS ONE. Apr 8 2020;15(4):e0231031. - PMC - PubMed
    1. Dacheux L MA, Ataman-Onal Y, Biron F, et al. Evolutionary dynamics of the glycan shield of the human immunodeficiency virus envelope during natural infection and implications for exposure of the 2G12 epitope. J Virol. Nov 2004;78(22):12625–37. - PMC - PubMed
    1. Grundner C PM, Kang JM, Koch M, et al. Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins. Virology. Dec 2004;330(1):233–48. - PubMed
    1. Berndsen ZT CS, Wang X, Cottrell CA, et al. Visualization of the HIV-1 Env glycan shieldacross scales. PNAS. Oct 22 2020;117(45):28014–25. - PMC - PubMed

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