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 of escape HIV variants


Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Inventors:

Li Liu (NIAID)  ➽ more inventions...

Bhavik Patel (NIAID)  ➽ more inventions...

Edward Berger (NIAID)  ➽ more inventions...

Richard Morgan (NCI)  ➽ more inventions...

Steven Rosenberg (NCI)  ➽ more inventions...


Intellectual Property:
US Application No. 15/039,384
PCT Application No. PCT/US2014/067459
US Application No. 61/908,691
International patent applications: Australia Patent Application No. 2014352638 filed November 25, 2014; Canada Patent Application No. 2930587 filed November 25, 2014; European Patent Application No. 14812376.3 filed June 13, 2016

Publications:

Dey B, et al.

PMID 12584309

Lagenaur LA, et al.

PMID 20158904

Berger EA.

PMID 21242898

Collaboration Opportunity:

Researchers at the NCI and NIAID seek licensing and/or co-development research collaborations for chimeric antigen receptors with high affinity for HIV env glyproteins.




Licensing Contact:
Benjamin Hurley, Ph.D.
Email: benjamin.hurley@nih.gov
Phone: 240-669-5092

OTT Reference No: E-170-2013/0
Updated: Oct 23, 2017