Feasibility evaluation of anti-HIV Antibody-secreting Chimeric Antigen Receptor T cells as a potential cure in acute seroconverters

30 March 2023 → 29 March 2024
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Medical and health sciences
    • Virology
Project description

Anti-HIV Chimeric Antigen Receptor (CAR) T cells have so far shown little success in human clinical trials. Initial studies demonstrated excellent toxicity profile with little-to-none adverse events, however efficacy was limited. Similar to observations from pioneering CAR-T trials in oncology field, lack of strong co-stimulation was possibly to blame. Recently, a broadly neutralizing antibody (bNAb) based CAR-T cells were shown to reduce proviral DNA load, however pre-existing resistance to the used VRC01 bNAb resulted in viral escape and fast rebound following analytical therapy interruption. HIV Cure Research Center has been developing improved, so called “Hybrid CAR T cells” which not only target the infected cells by CD4-ectodomain-madiated CAR killing, but also secrete broadly neutralizing antibodies to prevent replication of virions produced by the targeted cells and to mediate secondary immune functions via the Fc-receptor engagement. Our preliminary data indicates, that primary human T cells can be indeed modified to secrete functional, HIV-blocking antibodies while retaining the CAR-mediated killing. Within the context of proposed study we aim to investigate in vivo effects of the Hybrid CAR-T cells as well as to investigate the potential willingness – or lack of thereof – to undergo such treatment among people living with HIV. 

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Executive Agency (REA). Neither the European Union nor the authority can be held responsible for them.