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Advances in Therapeutic Targeting of Immune Checkpoints Receptors Within the Cd96-Tigit Axis: Clinical Implications and Future Perspectives Publisher Pubmed



Farhangnia P1, 2, 3 ; Akbarpour M3, 4 ; Yazdanifar M5 ; Aref AR6 ; Delbandi AA1, 7 ; Rezaei N2, 8, 9
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  3. 3. Immunology Board for Transplantation and Cell-Based Therapeutics (ImmunoTACT), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  4. 4. Advanced Cellular Therapeutics Facility (ACTF), Hematopoietic Cellular Therapy Program, Section of Hematology & Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, IL, United States
  5. 5. Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, United States
  6. 6. Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
  7. 7. Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran
  8. 8. Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
  9. 9. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Expert Review of Clinical Immunology Published:2022


Abstract

Introduction: The development of therapeutic antibodies targeting immune checkpoint molecules (ICMs) that induce long-term remissions in cancer patients has revolutionized cancer immunotherapy. However, a major drawback is that relapse after an initial response may be attributed to innate and acquired resistance. Additionally, these treatments are not beneficial to all patients. Therefore, the discovery and targeting of novel ICMs and their combination with other immunotherapeutics are urgently needed. Areas covered: There has been increasing evidence of the CD96-TIGIT axis as ICMs in cancer immunotherapy in the last five years. This review will highlight and discuss the current knowledge about the role of CD96 and TIGIT in hematological and solid tumor immunotherapy in the context of empirical studies and clinical trials, and provide a comprehensive list of ongoing cancer clinical trials on the blockade of these ICMs, as well as the rationale behind combinational therapies with anti-PD-1/PD-L1 agents, chemotherapy drugs, and radiotherapy. Moreover, we share our perspectives on anti-CD96/TIGIT-related combination therapies. Expert opinion: CD96-TIGIT axis regulates anti-tumor immune responses. Thus, the receptors within this axis are the potential candidates for cancer immunotherapy. Combining the inhibition of CD96-TIGIT with anti-PD-1/PD-L1 mAbs and chemotherapy drugs has shown relatively effective results in the context of preclinical studies and tumor models. © 2022 Informa UK Limited, trading as Taylor & Francis Group.
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