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.

Potential Commercial Applications: Competitive Advantages:
  • Therapy for HIV infection
  • Research on antiretroviral infection
  • Generate HIV-unsusceptible T cells
 
  • Target highly conserved regions of Env of HIV
  • Target non-MHC-expressing HIV-infected cells
  • Eliminate emergence escape HIV variants


Inventors:
Li Liu (NIAID)
Bhavik Patel (NIAID)
Edward Berger (NIAID)
Richard Morgan (NCI)
Steven Rosenberg (NCI)


Intellectual Property:
US Application No. 61/908,691

Publications:
Berger EA. PMID 21242898
Lagenaur LA, et al. PMID 20158904
Dey B, et al. PMID 12584309

Licensing Contact:
John Stansberry , Ph.D.
NIH Office of Technology Transfer
Email: js852e@nih.gov
Phone: 301-435-5236

OTT Reference No: E-170-2013/0

Updated: May-15-2014