123I Radiolabeled 3BNC117
Condition: Human Immunodeficiency Virus
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections
Study type: Interventional
Phase: Early Phase 1

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.
    

Detailed description: 
      The conventional way to control HIV infection is by use of a cocktail of drugs 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 and antiviral agents have no effect on these latently
      infected HIV cells.[1-9] Studies by Chomont et al. identified particular CD4 T cell subsets
      that serve as key cellular compartment for latent HIV-1 reservoir in blood.[6] A later study
      has identified memory CD4 T cells with stem-cell like properties as a minor latent HIV-1
      reservoir.[7] A major part of this reservoir is in the lymphoid tissue which constitute the
      predominant site for lymphocytes. One recent study has identified follicular T helper cells
      (TFH) of lymph nodes as major CD4 T cell compartments for HIV-1 replication, production and
      infection.[8] Further characterisation of the different CD4 T cell population has identified
      a specific cell population expressing PD-1(+) as the major CD4 T cell compartment in blood
      and lymph nodes for production of replication competent and infectious HIV-1.[9] Thus,
      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 use of
      currently used drugs capable of suppressing and thereby controlling the viral replication
      cycle in HIV infected patients.

      As discussed above, even though ART can suppress virus replication and can limit disease
      progression, it fails to eradicate the virus, and suppression requires lifelong therapy,
      which may have side effects and poses a risk of the development of resistance. New approaches
      necessary to prevent and treat HIV-1 infection in order to restrict the epidemic and to
      strengthen nascent efforts in finding a cure are gradually emerging. A new generation of
      highly potent broadly neutralizing antibodies (bNAbs) may represent a promising approach to
      combating HIV-1 infection.[10] Many sites on the viral envelope can be recognized by bNAbs.

      The broadly neutralising antibody 3BNC117 directed against the HIV gp120 envelope protein,
      can mimic human CD4 binding and can neutralize 195 out of 237 HIV-1 strains.[11] The first
      human phase I dose escalation study using 3BNC117, has shown to be safe and effective in
      transiently reducing viraemia in chronic HIV-1 infected individuals.[12] A subsequent study
      (ClinicalTrial.gov identifier:NCT02018510) demonstrated improved host humoral immune response
      in infected individuals treated with 3BNC117 antibody as compared to untreated
      individuals.[13] Furthermore, a phase IIa open labelled trial by the same group of
      researchers at Rockefeller University, NY has been carried out to evaluate the capacity of
      this antibody to suppress viral rebound in infected individuals during a brief treatment
      interruption of anti-retroviral therapy.[14] Another such trial is currently ongoing
      (ClinicalTrial.gov identifier: NCT02446847).

      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 in vitro for gp120. By using state of
      the art SPECT scanner a semi-quantitative image will be obtained. In addition, the well known
      use of iodine-123 in clinic and the absence of chelator makes it suitable for human
      intervention.

      No HIV imaging in human has yet been achieved, which is however fundamental to understand
      some key steps in the pathogenesis of the HIV-induced immunodeficiency. This research opens
      promising opportunities for monitoring the size of the HIV reservoir and 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.
    

Intervention name(s): 123I radiolabeled 3BNC117
Intervention type(s): Combination Product
Intervention description(s): 123I radiolabeled 3BNC117
Intervention model: Single Group Assignment
Intervention model description: Monocentric, open-label and uncontrolled study
Masking: None (Open Label)
Primary purpose: Basic Science