Trispecific antibodies show exceptionally promising results against HIV.
In a landmark study, the National Institutes of Health (NIH) and Sanofi researchers produced genetically engineered antibodies (Abs) with the greatest activity and coverage seen against human immunodeficiency virus (HIV-1).
Natural Abs recognize a single target on a foreign protection, however, in this study, the Abs were engineered to recognize 3 different target sites in 1 molecule. The trispecific Abs were highly effective in suppressing virus growth and infection.
“Combination therapy has already demonstrated its value in HIV and cancer therapy,” Gary Nabel (pictured), MD, PhD, chief scientific officer, senior vice president, Sanofi, and lead co-author of the study said. “Trispecific antibodies represent a potential new class of therapeutics that can block multiple targets with a single agent. This new approach supports a central pillar of Sanofi’s strategy to use multi-targeting to develop transformative medicines for incurable diseases.”
While using broadly neutralizing HIV Abs to tackle the ongoing pandemic, a key challenge is to overcome the genetic diversity of viruses around the world. Trispecific Abs showed greater coverage than any previously-studied Ab — neutralizing 99% of more than 200 diverse HIV-1 strains.
Researchers engineered trispecific Abs allowing a single molecule to interact with 3 independent HIV-1 envelope determinants: the CD4 binding site, the membrane proximal external region (MPER) and the V1V2 glycan site.
Trispecific Abs exhibited higher potency and breadth than previously described single broadly neutralizing Abs (bnAb) and showed pharmacokinetics similar to human bnAbs and conferred complete immunity against a mixture of Simian-Human Immunodeficiency Virus (SHIVS) in non-human primates (NHP) in comparison to single bnAbs.
The Abs constitute a platform to engage multiple therapeutic targets through a single protein, potentially applicable for diverse diseases like infections, cancer and autoimmunity.
Sanofi is currently manufacturing the trispecific Ab for use in a phase 1 clinical trial, expected to begin in 2018, at the National Institute of Allergy and Infectious Diseases (NIAID). The trispecific Abs are in preclinical development. Their safety and efficacy have not yet been fully evaluated.
A press release has been made available.