123I Radiolabeled 3BNC117

Summary

The conventional way to control HIV infection is the usage of a drug cocktail capable of suppressing the viral replication cycle, commonly known as antiretroviral therapy (ART). Despite effective ART it is not possible to eradicate HIV. The virus hides in particular cells to form the latent HIV-reservoir.\[1-9\] Studies that emphasise on revealing hidden reservoirs would aid in designing novel therapeutic strategies for controlling HIV infection. Molecular imaging by SPECT/CT has the potential to reveal hidden reservoirs of HIV virus that are not eliminated by currently used drugs capable of suppressing and thereby controlling the viral replication cycle in HIV infected patients. New approaches, necessary to prevent and treat HIV-1 infection, are gradually emerging. A new generation of highly potent broadly neutralizing antibodies (bN/Abs) may represent a promising approach to combating HIV-1 infection.\[10\] The broadly neutralizing antibody 3BNC117 antibody that can mimic human CD4 binding targeted against the HIV gp120 envelope protein has been tested in various clinical trials.\[11-14\] It has found to be safe and effective in reducing viraemia and to improve host humoral responses in HIV-1 infected individuals, and to have effect on viral rebound in patients who are kept off antiretroviral treatment briefly for experimental purpose. Imaging of simian immunodeficiency virus (SIV) infection by PET/CT has been successfully performed in nonhuman primates with a 64Cu-labeled SIV gp120-specific antibody called 7D3.\[15\] This study aims to use a similar approach in human with the 3BNC117 antibody. The 3BNC117 antibody has been successfully radiolabeled with iodine 123. The half-life of this radioisotope is appropriate for antibody imaging in nuclear medicine. Radiolabeled 123I 3BNC117 was shown to keep a good immunoreactivity for gp120. By using state of the art SPECT scanner a semi-quantitative image will be obtained. In addition, the absence of any chelator and the well known use of iodine-123 in clinic make it suitable for human intervention. No HIV imaging in human has been achieved yet, which is however fundamental to understand some key steps in the pathogenesis of HIV-induced immunodeficiency. This research opens promising opportunities for drug and vaccine development. Indeed, identification of virus reservoirs in treated patients would facilitate the development of strategies for eradicating these reservoirs or for extending latency period.

Timeline

Start

2018-02-08

Primary completion

2020-01-28

Completion

2020-01-28

Publications

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• Background Schoofs T, Klein F, Braunschweig M, Kreider EF, Feldmann A, Nogueira L, Oliveira T, Lorenzi JC, Parrish EH, Learn GH, West AP Jr, Bjorkman PJ, Schlesinger SJ, Seaman MS, Czartoski J, McElrath MJ, Pfeifer N, Hahn BH, Caskey M, Nussenzweig MC. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science. 2016 May 20;352(6288):997-1001. doi: 10.1126/science.aaf0972. Epub 2016 May 5.
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