Multi-specific Chimeric Antigen Receptors Against HIV
The present disclosure is directed to novel CD4-based multi-specific chimeric antigen receptor (CAR) proteins composed of an extracellular targeting moiety containing at least two HIV Env-binding motifs, linked to a transmembrane domain and a cytoplasmic signaling domain. The invention further discloses nucleic acids encoding the novel chimeric antigen receptors to enable their expression in host T cells for treatment of HIV infection and disease. Importantly, CAR-transduced CD8 T cells recognize HIV-infected target cells in MHC independent fashion by binding the highly conserved regions of the HIV Env glycoprotein, thus minimizing the selection of viral escape mutants. Furthermore, the present invention also relates to methods of generating a recombinant CD8 T cells expressing a CAR with a CD4-based targeting moiety that does not confer susceptibility to HIV infection.
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Li Liu (NIAID)
Bhavik Patel (NIAID)
Edward Berger (NIAID)
Richard Morgan (NCI)
Steven Rosenberg (NCI)
US Application No. 61/908,691
Berger EA. PMID 21242898
Lagenaur LA, et al. PMID 20158904
Dey B, et al. PMID 12584309
John Stansberry , Ph.D.
NIH Office of Technology Transfer
OTT Reference No: E-170-2013/0