The Use of Chimeric Antigen Receptor to Control HIV Infection


Chimeric Antigen Receptors (CARs) are engineered proteins expressed by transduction on autologous CD8 T cells; after adoptive transfer, they promote targeted killing of specific cell types. CARs are showing great promise for treating cancer. The present invention (CD4-CRD CAR) is a novel bifunctional targeting motif for an anti-HIV CAR, consisting of a region of human CD4 linked to a carbohydrate recognition domain (CRD) from one of several human C-type lectins known to interact with high-mannose glycans on HIV gp120. Compared to a “standard” CD4 CAR, the CD4-CRD CAR displays two major enhancements: 1) increased potency for suppression of HIV-1 infection by selective killing of productively infected cells, and 2) complete absence of CD4-mediated entry receptor activity that would otherwise render the transduced CD8 T cells susceptible to HIV infection. Compared to antibody-based anti-HIV CARs, the CD4-CRD CAR of the present invention is predicted to have two major advantages: 1) Lower escape potential, due to the universality of HIV CD4-dependence and high-mannose glycan display on gp120, and 2) reduced immunogenicity, since the all-human CD4-CRD CAR sequences are devoid of variable regions that would likely elicit anti-idiotypic antibody responses against scFv-based targeting motifs.

Potential Commercial Applications: Competitive Advantages:
  • Therapy for HIV infection
  • Research on antiretroviral infection
 
  • Enhanced potency for HIV inhibition and does not render transduced CD8T cells susceptible to HIV infection.


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


Inventors:

Mustafa Ghanem (NIAID)  ➽ more inventions...

Barna Dey (NIAID)  ➽ more inventions...

Edward Berger (NIAID)  ➽ more inventions...


Intellectual Property:
US Application No. 62/040,398

Publications:
Scholler J, et al. PMID 22553251
Du T, et al. PMID 22687513
Lamers CH, et al. PMID 20889925

Collaboration Opportunity:

The National Institute of Allergy and Infectious Diseases is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize this technology. For collaboration opportunities, please contact Chris Kornak at chris.kornak@nih.gov.


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

OTT Reference No: E-212-2014/0
Updated: Sep 9, 2015