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The potential of engineered antibodies for HIV-1 therapy and cure
Marloes Grobben1, Richard Al Stuart1, Marit J van Gils1
1Department of Medical Microbiology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, 1105 AZ, The Netherlands.
Broadly neutralizing antibodies (bnAbs) are currently under investigation as a therapy for HIV-1 infection and recent clinical trials have shown prolonged viral suppression by bnAbs during antiretroviral treatment interruption. Interestingly, these bnAbs also showed the ability to activate the host immune system to clear HIV-1 infected cells. There are many possibilities to further increase the potential efficacy of bnAbs. Most notably, Fc domain engineering to improve half-life and increase engagement of effector cells will augment two advantages of bnAbs. Moreover, antibody engineering can improve affinity and recognition of conserved epitopes and allows the combination of multiple epitope specificities in a single molecule. These increasingly potent and broad antibodies may prove valuable as alternative HIV-1 therapeutic and possibly in curative approaches.
Broadly neutralizing antibodies (bnAbs) are currently under investigation as a therapy for HIV-1 infection and recent clinical trials have shown prolonged viral suppression by bnAbs during antiretroviral treatment interruption. Interestingly, these bnAbs also showed the ability to activate the host immune system to clear HIV-1 infected cells. There are many possibilities to further increase the potential efficacy of bnAbs. Most notably, Fc domain engineering to improve half-life and increase engagement of effector cells will augment two advantages of bnAbs. Moreover, antibody engineering can improve affinity and recognition of conserved epitopes and allows the combination of multiple epitope specificities in a single molecule. These increasingly potent and broad antibodies may prove valuable as alternative HIV-1 therapeutic and possibly in curative approaches.
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