A radiolabeled mAb 3BNC117 with copper-64: First round in favor for studying clearance of HIV reservoirs

Abstract

The article published by McMahon and colleagues [1] reports the first clinical trial in humans using a monoclonal neutralizing antibody (mAb) attached to a detection system with radioisotopes and measured by positron-emission tomography (PET) to assess the neutralizing effect of the mAb among the potential reservoirs of human immunodeficiency virus (HIV) in volunteers with and without HIV infection. The series of experiments implemented by the team shows the effort invested to obtain all measurements with the highest accuracy and precision crucial for this sort of studies. The most important similar study previously implemented used a poly(ethylene glycol)modified, (64) Cu-labelled Simian Immunodeficiency Virus (SIV) Gp 120-specific antibody and was reported by Santangelo and his group [2]. They reported the dynamics of SIV in the whole body of viremic and under antiretroviral therapy (ART) treatment macaques using an antibody-targeted PET (immunoPET). An experiment, which until that time, was limited to biopsies and autopsies. These experiments showed detectable signals in important organs higher signals among viremic macaques and lower in macaques under-ART. These results promised better approaches for the study of HIV pathogenesis, opening doors for the development of new drugs and vaccines. In the initial stages of its development, immunotherapy against HIV was mostly inadequate, subsequent successes were achieved when cloning methods of antibodies based on single cells were further developed. These antibodies have a higher neutralizing effect, can prevent HIV infection and suppress the viremia in humanized mice and non-human primates, but until Santangelo’s study we have not had indications of how to use this effect for immunotherapy. Caskey et al., reported the use of the mAb 3BNC117, a specific antibody directed against the CD4 receptor in a phase 1 clinical trial in humans [3], her work showed a reduction in viral load among persons living with HIV. This effect lasted for 28 days after injection in some cases. The same team years later, also showed that the use of combined