Dixon et al. generated agonistic and blocking anti-mouse antibodies (Abs) against the coinhibitory receptor TIGIT that modulated T cell response. In mice, agonistic anti-TIGIT Abs reduced the severity of autoimmune disease. Antagonistic anti-TIGIT Ab combined with anti-PD-1 improved tumor control in mice with colon carcinoma or glioblastoma by enhancing T cell proliferation, antitumor cytokine production, and long-term immunity.
Coinhibitory receptors, such as CTLA-4 and PD-1, play a critical role in maintaining immune homeostasis by dampening T cell responses. Recently, they have gained attention as therapeutic targets in chronic disease settings where their dysregulated expression contributes to suppressed immune responses. The novel coinhibitory receptor TIGIT (T cell Ig and ITIM domain) has been shown to play an important role in modulating immune responses in the context of autoimmunity and cancer. However, the molecular mechanisms by which TIGIT modulates immune responses are still insufficiently understood. We have generated a panel of monoclonal anti-mouse TIGIT Abs that show functional properties in mice in vivo and can serve as important tools to study the underlying mechanisms of TIGIT function. We have identified agonistic as well as blocking anti-TIGIT Ab clones that are capable of modulating T cell responses in vivo. Administration of either agonist or blocking anti-TIGIT Abs modulated autoimmune disease severity whereas administration of blocking anti-TIGIT Abs synergized with anti-PD-1 Abs to affect partial or even complete tumor regression. The Abs presented in this study can thus serve as important tools for detailed analysis of TIGIT function in different disease settings and the knowledge gained will provide valuable insight for the development of novel therapeutic approaches targeting TIGIT.
Author Info: (1) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (2) Institute of Ex
Author Info: (1) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (2) Institute of Experimental Immunology, University of Zurich, Zurich CH-8057, Switzerland. (3) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (4) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (5) Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114. (6) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (7) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (8) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (9) Palo Alto Veterans Administration Health Care System, Palo Alto, CA 94304; and. Department of Pathology, Stanford University School of Medicine, Stanford, CA (10) Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114. (11) Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114. (12) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA (13) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA 02115; nicole.joller@immunology.uzh.ch vkuchroo@evergrande.hms.harvard.edu. (14) Evergrande Center for Immunologic Diseases at Harvard Medical School and Brigham and Women's Hospital, Ann Romney Center for Neurologic Diseases, Boston, MA 02115; nicole.joller@immunology.uzh.ch vkuchroo@evergrande.hms.harvard.edu. Institute of Experimental Immunology, University of Zurich, Zurich CH-8057, Switzerland.
