About “Immunotherapy 〜Immune checkpoint inhibitor〜”

 

　Profile #4: Dr. KONNAI Satoru, Professor

　1) Laboratory of Infectious Diseases, Department of Disease Control,

　2) Department of Advanced Pharmaceutics, 

　Faculty of Veterinary Medicine

 

　【Research Topics】

　・Drug discovery research on refractory diseases in animal

 

 

「Immunotherapy〜Immune checkpoint inhibitor〜」

 

In recent years, it has been suggested that various immune checkpoint molecules are involved in the progression and maintenance of refractory diseases, such as chronic infections and cancer, and these have been shown to constitute a part of the mechanism allowing immune evasion by infected cells and tumor cells. In such diseases, immunosuppressive factors, such as programmed death 1 (PD-1), are expressed on effector cells at increased levels and bind to their respective ligands to induce immune exhaustion of the effector cells. This results in markedly reduced cell proliferation, cytokine production and cytotoxic activity. However, as this reaction is reversible, antibody-based means to inhibit the immune checkpoint function are being studied. For example, the administration of anti-programmed death-ligand 1 (PD-L1) or anti-PD-1 antibodies capable of suppressing PD-1 signaling has been reported to enhance the proliferation and cytokine production of pathogen- or tumor-specific T cells as well as the expression of effector molecules. Thus, the immune checkpoint inhibitor is anticipated to be applicable as a new therapeutic strategy for the refractory diseases. For use in humans, several immune checkpoint inhibitors have been successively developed for cancer immunotherapy. In 2018, the Nobel Prize in Physiology or Medicine was awarded jointly to Dr. Tasuku Honjo, a professor in Kyoto University and Dr. James P. Allison for their discovery of cancer therapy by the immune checkpoint inhibitors. However, such studies have been still limited in the fields of veterinary medicine. Recent studies in our laboratory have revealed that several immune checkpoint molecules play critical roles in immune exhaustion and disease progression in refractory diseases without effective vaccine. Among them, we are currently conducting clinical researches on the bovine leukemia virus infection, bovine mycoplasmosis, and canine cancers by using the immune checkpoint inhibitors. In the future, it is anticipated that immune checkpoint inhibitors will be applied to veterinary medicine.　

 

Research Press Release:

・New therapeutic antibody for dog cancers

https://www.global.hokudai.ac.jp/blog/new-therapeutic-antibody-for-dog-cancers/

https://www.global.hokudai.ac.jp/wp-content/uploads/2017/09/HUTimes_Issue3.pdf

・Overcoming immune suppression to fight against bovine leukemia

https://www.global.hokudai.ac.jp/blog/overcoming-immune-suppression-to-fight-against-bovine-leukemia/

・The drug combination effective against bovine leukemia

https://www.global.hokudai.ac.jp/blog/the-drug-combination-effective-against-bovine-leukemia/

・Unraveling the immunopathogenesis of Johne’s disease

https://www.global.hokudai.ac.jp/blog/unraveling-the-immunopathogenesis-of-johnes-disease/

・Developing immunotherapy to save animals | Research Highlight | Hokkaido University (April 08, 2019)

https://www.global.hokudai.ac.jp/blog/developing-immunotherapy-to-save-animals/

・Japan’s global connectors (Nature 567(7748), S12-S17 (21 March 2019))

https://www.nature.com/articles/d41586-019-00831-5