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Novel Anti-PD1 Antibodies for Inhibiting T-cell Activity
Boston Children's Hospital
Antibody
Immunology
Target Identification or Validation
Unmet Medical Needs
PD1 (Programmed Death 1) is an
immune checkpoint protein that negatively regulates immune system activity
through its interaction with PD ligands. In cancer, inhibition of the PD1/PD
ligand interaction by anti-PD1 antibodies has been harnessed as an effective
therapeutic strategy to boost immune attack against tumors. On the other hand,
stimulating the PD1 pathway by therapeutic antibodies could potentially suppress
deleterious immune activities in autoimmune diseases, and there is currently a
shortage of such PD1 agonist antibodies.
Technology Description
Dr. Frederick Alt’s lab at Boston Children’s Hospital generated novel humanized anti-PD1 antibodies, using an
in vivo mouse model of antibody diversification that harnesses the natural
affinity maturation processes. Some of these new anti-PD1 antibodies can
enhance, rather than inhibit, PD1 interaction with its ligand,
PD-L1.
Technology Proof of Concept
• A PD-1 expressing cell line was incubated with PD-L1 or PD-L1 plus an anti-PD1 antibody
• Original anti-PD1 antibody before diversification inhibited binding of PD-L1 to PD1 whereas the newly diversified anti-PD1 antibody enhanced PD1/PD-L1 interaction.
Potential Commercial Applications
The effects of these PD1/PD-L1
enhancing antibodies on T cell activities remain to be validated in animal
models. If these antibodies can indeed suppress T cell activity in vivo,
they could potentially be developed into therapeutics for autoimmune diseases,
in which destructive T cell activities play a major role, such as in type 1
diabetes and rheumatoid arthritis.
Competitive Advantages
These novel anti-PD1 antibodies were isolated from mouse models, where antibodies with poly-reactivities and unstable conformations are eliminated by quality control systems in vivo. Such antibodies may be more amenable to clinical application.
Ming Tian, Hwei-Ling Cheng
PCT-US2021-041407 (2021.07.13)
Patent Family: EP
"An in vivo method for diversifying the functions of therapeutic antibodies". Ming Tian, et al. Proc Natl Acad Sci USA. 2021 Mar 9;118(10):e2025596118.
