Immune Correlate + Guided Design of Monoclonal Therapeutics for HIV Remission
Abstract
Human immunodeficiency virus (HIV) care has experienced a dramatic revolution over the past decade due to new evidence that a cure for HIV may be possible. One instance of a functional cure has been reported in humans in a patient in Berlin following bone marrow transplantation with an HIV-co-receptor deficient bone marrow graft. However, while bone marrow transplantation is not a viable means to cure all those afflicted with the disease globally, efforts have focused on the development of chemotherapeutics that may “specifically” purge the body of infected cells. Among the approaches, the use of monoclonal therapeutics has gained tremendous traction due to the remarkable success of antibody-drugs in the oncology and autoimmunity fields, where long phases of remission, and even cure, have been observed. The success of these biological drugs pertains to their ability to recognize their target with exquisite and high specificity, and then either block the biological activity of the target or drive the deletion of the target via the recruitment of innate cytotoxic activity. Along these lines, dozens of monoclonal antibodies that target HIV global viral variants broadly with remarkable affinity exist and have been tested for their ability to target and eradicate the viral reservoir in preclinical and clinical models. While several of these antibodies have shown tremendous promise at reducing viremia in vivo, the virus always rebounds rapidly, strongly arguing that while these therapeutics are remarkably effective at targeting the virus, they target infected cells – that harbor the virus – very poorly. The underlying explanation for this failure is simply related to the fact that these antibodies are selected for their capacity to recognize the virus, but not the infected cell, which may harbor the viral envelope in a different conformation/context. Thus, here we aim to develop a novel class of “HIV cure” antibodies, focused on the identification of both the key specificities and functions of protective antibodies that target the cellular-viral reservoir. Using cohorts of individuals that show some unique ability to target or control their cellular-viral reservoir, this collaborative team will design and engineer a novel class of monoclonal therapeutics to directly drive long-term remission of HIV infection or provide a roadmap for the design of a therapeutic vaccine that may end the devastation cause by this infectious disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810579
Entities
People
- Galit Alter
Organizations
- Massachusetts General Hospital
- United States Army