B cell engineering and clinical core

ABSTRACT The B Cell Engineering and Clinical Core aims to develop autologous human B cell engineering for sustained antibody expression to address the limited persistence of broadly neutralizing antibodies (bnAbs) against HIV. These bnAbs can suppress viremia in persons with HIV (PWH) off antiretroviral therapy (ART), but their short mean elimination half-lives allow for viral rebound and resistance development. We will collect and engineer tissues from mice, non-human primates (NHPs), and PWH. This core will provide essential biological samples and characterization for the proposed scientific projects, facilitating the development of engineered B cells to enhance bnAb efficacy and longevity. The core’s specific aims are: 1. Provide primary samples from PWH and characterize sensitivity to bnAbs and viral isolates. 2. Optimize IgH-reprogramming in NHP B cells. 3. Provide mouse, NHP, and human IgH- reprogrammed B cells. 4. Conduct preliminary characterization of human IgH-reprogrammed B cells. Human tissues will be supplied to Project 4 for organoid models, mice tissues to Project 2 using the B6 mouse model, and NHP tissues to Project 3. Mouse and NHP tissues will also be provided to Project 4. Human work will leverage samples and clinical data from ‘The Last Gift’ cohort, consisting of altruistic PWH on ART with terminal illnesses who donate their bodies. For mouse and NHP work, we will collaborate with Tabby Therapeutics, which specializes in innovative B cell engineering therapies, including for HIV. Their comprehensive approach involves meticulous IgH-reprogramming of B cells across species, ensuring efficacy, safety, and translational potential. These resources will generate key data for the proposed projects, advancing the development of sustained HIV remission therapies by enhancing bnAb persistence and addressing resistance challenges.