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RESEARCH PRODUCT
Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells
Shoichi MaruyamaShinko HayashiTeiji WadaDaisuke SugiyamaMichinori KadokuraAtsushi TanemuraKazuki HiraharaMasato AmanoIchiro WatanabeShiho KozumaMegumi MiyamotoKenichi WakitaAtsushi OkamotoMasato HataKazuki SatohTakahiko SatoSaori IshidaHiroyoshi NishikawaHelmut JonuleitToshinori AgatsumaYoichi KobayashiAndrea TuettenbergKyungtaek LimKaori Fujimakisubject
0301 basic medicinemedicine.drug_classmedicine.medical_treatmentImmunologychemical and pharmacologic phenomenaMice SCIDBiologyMonoclonal antibodyT-Lymphocytes RegulatoryMice03 medical and health sciences0302 clinical medicineImmune systemCancer immunotherapyMice Inbred NODImmunityNeoplasmsImmune ToleranceTumor MicroenvironmentmedicineAnimalsHumansImmunology and AllergyMice KnockoutTumor microenvironmentImmunityAntibodies MonoclonalMembrane ProteinsFOXP3General MedicineImmunosurveillance030104 developmental biology030220 oncology & carcinogenesisLeukocytes MononuclearCancer researchbiology.proteinFemaleImmunotherapyAntibodydescription
Abstract Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-04-30 | International Immunology |