Article ; Online: FS222, a CD137/PD-L1 Tetravalent Bispecific Antibody, Exhibits Low Toxicity and Antitumor Activity in Colorectal Cancer Models.
Clinical cancer research : an official journal of the American Association for Cancer Research
2020 Volume 26, Issue 15, Page(s) 4154–4167
Abstract: Purpose: With the increased prevalence in checkpoint therapy resistance, there remains a significant unmet need for additional therapies for patients with relapsing or refractory cancer. We have developed FS222, a bispecific tetravalent antibody ... ...
| Abstract | Purpose: With the increased prevalence in checkpoint therapy resistance, there remains a significant unmet need for additional therapies for patients with relapsing or refractory cancer. We have developed FS222, a bispecific tetravalent antibody targeting CD137 and PD-L1, to induce T-cell activation to eradicate tumors without the current toxicity and efficacy limitations seen in the clinic. Experimental design: A bispecific antibody (FS222) was developed by engineering CD137 antigen-binding sites into the Fc region of a PD-L1 IgG1 mAb. T-cell activation by FS222 was investigated using multiple Results: We demonstrated simultaneous binding of CD137 and PD-L1 and showed potent T-cell activation across CD8 Conclusions: By targeting CD137 agonism to areas of PD-L1 expression, predominantly found in the tumor microenvironment, FS222 has the potential to leverage a focused, potent, and safe immune response augmenting the PD-(L)1 axis blockade. |
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| MeSH term(s) | Animals ; Antibodies, Bispecific/physiology ; Antibodies, Bispecific/therapeutic use ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; Cell Line, Tumor/transplantation ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Disease Models, Animal ; Drug Screening Assays, Antitumor ; Female ; HEK293 Cells ; Humans ; Leukocytes, Mononuclear ; Macaca fascicularis ; Mice ; Primary Cell Culture ; Tumor Microenvironment/drug effects ; Tumor Microenvironment/immunology ; Tumor Necrosis Factor Receptor Superfamily, Member 9/antagonists & inhibitors | |||||
| Chemical Substances | Antibodies, Bispecific ; Antineoplastic Agents, Immunological ; B7-H1 Antigen ; CD274 protein, human ; TNFRSF9 protein, human ; Tumor Necrosis Factor Receptor Superfamily, Member 9 | |||||
| Language | English | |||||
| Publishing date | 2020-04-28 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1225457-5 | |||||
| ISSN | 1557-3265 ; 1078-0432 | |||||
| ISSN (online) | 1557-3265 | |||||
| ISSN | 1078-0432 | |||||
| DOI | 10.1158/1078-0432.CCR-19-2958 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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