BTN3A Ectodomain Proteins and Methods of Use
Patent Number: US20180147257A1
Executive Summary:
General Description:
Once T cells have been presented with a foreign antigen, they must also be exposed to a co-stimulatory molecule before they will attack that antigen. Butrophyllin Butyrophilin 3A1 (BTN3A1, or CD277 is a naturally occurring molecule in the human body that is upregulated when cells are stressed. Recombinant BTN3A1 has been shown to act as a co-stimulatory molecule that activates T cells through the T-cell receptor. Administration of the recombinant BTN3A1 with antibodies targeting tumor cells or invading pathogens can increase T cell response and contribute to clearance of the tumor cell or pathogen.
Scientific Progress:
A method to activate T-cells that has not yet been described.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Legal status: Pending
Publication PMID: 26907590
Publication:
McGuire AT, Gray MD, Dosenovic P, Gitlin AD, Freund NT, Petersen J, Correnti C, Johnsen W, Kegel R, Stuart AB, Glenn J, Seaman MS, Schief WR, Strong RK, Nussenzweig MC, Stamatatos L. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat Commun. 2016 Feb 24;7:10618.
Inventor Bio: Irving Weissman
https://profiles.stanford.edu/irving-weissman
Executive Summary:
- Invention Type: Therapeutic and Diagnostic
- Patent Status: Pending
- Patent Link: https://patents.google.com/patent/US20180147257A1
- Related Patent Link: https://patents.google.com/patent/WO2016191305A1
- Research Institute: Stanford University
- Disease Focus: Brain tumors
- Basis of Invention: T cells must be activated to fight infection or other diseases, like cancer. They must be stimulated by an antigen presented by an antigen producing cell (APC) and by a co-stimulatory molecule on the surface of another T cell or an APC. There must be a co-stimulatory signal to complement recognition of an antigen; without it, the T cell will not mount an immune response
- How it works: The BTN3A ectodomain polypeptide stimulates APC activity, which provides the co-stimulatory signal required for a T cell to mount an attack after being presented with an antigen
- Lead Challenge Inventor: Irving Weissman
- Inventors: Daniel Mark Corey, Aaron Michael Ring, Irving Weissman
- Development Stage: Lead Optimization
- Novelty:
- Potential to stimulate or suppress immune responses in humans
- Additional pathway that provides costimulatory signals to T cells that has not previously been elucidated
- Clinical Applications:
- Modulating T cell and antibody-mediated immune responses in cancers, infectious diseases, and autoimmune diseases
- Could be used to complement or further enhance immunostimulatory agents such as anti-PD-1, anti-CTLA4, interleukin02, anti-CD47, etc.
- Given that the recombinant BTN3A1-Fc protein is inert when administered in the absence of TCR stimulation, it could be useful as an adjuvant to vaccines, to BiTE (bispecific T cell engaging) antibodies, or to CAR (chimeric antigen receptor)/ TCR-engineered T cells
- Blocking the interaction could be useful in the setting of organ transplantation to inhibit organ graft rejection or autoimmune disease
General Description:
Once T cells have been presented with a foreign antigen, they must also be exposed to a co-stimulatory molecule before they will attack that antigen. Butrophyllin Butyrophilin 3A1 (BTN3A1, or CD277 is a naturally occurring molecule in the human body that is upregulated when cells are stressed. Recombinant BTN3A1 has been shown to act as a co-stimulatory molecule that activates T cells through the T-cell receptor. Administration of the recombinant BTN3A1 with antibodies targeting tumor cells or invading pathogens can increase T cell response and contribute to clearance of the tumor cell or pathogen.
Scientific Progress:
A method to activate T-cells that has not yet been described.
Future Directions:
- Preclinical testing in rodent models; clinical validation in humans
Strengths:
- Can strengthen or weaken immune response in humans
Weaknesses:
- Many co-stimulatory molecules are being investigated to activate T cells
- This invention has not been tested in vivo
Patent Status:
Legal status: Pending
- Priority date: 2015-05-22
- Filing date: 2016-05-20
- Publication date: 2018-05-31
Publication PMID: 26907590
Publication:
McGuire AT, Gray MD, Dosenovic P, Gitlin AD, Freund NT, Petersen J, Correnti C, Johnsen W, Kegel R, Stuart AB, Glenn J, Seaman MS, Schief WR, Strong RK, Nussenzweig MC, Stamatatos L. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat Commun. 2016 Feb 24;7:10618.
Inventor Bio: Irving Weissman
https://profiles.stanford.edu/irving-weissman
