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. 2022 Aug 28;8(3):100083.
doi: 10.1016/j.jve.2022.100083. eCollection 2022 Sep.

Bispecific antibody-derived molecules to target persistent HIV infection

Jeffrey L Nordstrom  1 , Guido Ferrari  2   3 , David M Margolis  4
Affiliations

Bispecific antibody-derived molecules to target persistent HIV infection

Jeffrey L Nordstrom et al. J Virus Erad. .

Abstract

HIV infection persists despite durable and potent antiviral therapy. To target persistent HIV infection, one major strategy aims to induce HIV provirus expression using latency reversing agents and then eliminate these reservoir cells via immune responses enhanced by treatment with antibody-derived bispecific molecules. The specificities of anti-HIV-1 envelope monoclonal antibodies have been incorporated into bispecific molecules that can recognize infected cells and recruit cytotoxic immune cells to eliminate them. This concept seeks to engineer a unique and potent effector response based on the opportunity to target conserved viral epitopes on infected cells, and recruit broad populations of immune effector cells that are not limited by major histocompatibility complex restrictions or other programmed specificity constraints. This article provides a review of bispecific DART® molecules and other dual-specificity antibody-based molecules that function by co-engaging CD3-expressing T cells or CD16A-expressing NK cells with HIV-1-infected cells.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
DART molecule structure and mechanism for redirected CD3+T cell-mediated cytolysis of HIV-1-infected Env-expressing cells. The anti-CD3 arm (orange) binds to CD3 (brown) at the surface of CD3+ T cells (effector cell), and the anti-HIV-1 env arm (dark blue) binds to HIV-1 Env at the surface of HIV-1 infected CD4+ T cells (target cell). Cell surface HIV-1 Env glycoprotein (light blue) may be in the form of functional mature trimers or nonfunctional variant forms such as gp160 monomers or gp41 stumps. DART molecule-mediated co-engagement of target and effector cells results in activation of CD3+ T cell-mediated cytolytic responses against Env-expressing target cells. The human IgG1 Fc domain (grey), which is inactivated for FcγR binding but retains FcRn binding, is included to confer an extended circulating half-life in vivo. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)
See this image and copyright information in PMC

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References

    1. Halper-Stromberg A., Nussenzweig M.C. Towards HIV-1 remission: potential roles for broadly neutralizing antibodies. J Clinic Invest. 2016;126:415–423. - PMC - PubMed
    1. Lambotte O., Pollara J., Boufassa F., et al. High antibody-dependent cellular cytotoxicity responses are correlated with strong CD8 T cell viral suppressive activity but not with B57 status in HIV-1 elite controllers. PLoS One. 2013;8 - PMC - PubMed
    1. Lambotte O., Ferrari G., Moog C., et al. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS. 2009;23:897–906. - PMC - PubMed
    1. Ackerman M.E., Mikhailova A., Brown E.P., et al. Polyfunctional HIV-specific antibody responses are associated with spontaneous HIV control. PLoS Pathog. 2016;12 e1005315-14. - PMC - PubMed
    1. Scheid J.F., Horwitz J.A., Bar-On Y., et al. HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature. 2016;535:556–560. - PMC - PubMed

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