Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4
Abstract Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA‐4, is successful in clinical use. However, it is associated with a high incidence of adverse events, and its therapeutic efficacy needs improving. In this study, polymeric multivalent Fc‐binding peptides (P...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202408899 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832593550141816832 |
|---|---|
| author | Zongyu Liu Hongyu Chu Weidong Zhao Chenguang Yang Tongjun Liu Na Shen Zhaohui Tang |
| author_facet | Zongyu Liu Hongyu Chu Weidong Zhao Chenguang Yang Tongjun Liu Na Shen Zhaohui Tang |
| author_sort | Zongyu Liu |
| collection | DOAJ |
| description | Abstract Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA‐4, is successful in clinical use. However, it is associated with a high incidence of adverse events, and its therapeutic efficacy needs improving. In this study, polymeric multivalent Fc‐binding peptides (PLG‐Fc‐III‐4C) are employed to fabricate a bispecific antibody (PD1/CTLA‐4 BsAb) to potentiate dual immunotherapy targeting PD1 and CTLA‐4. The PD1/CTLA‐4 BsAb is prepared by mixing PLG‐Fc‐III‐4C with aPD1 and aCTLA‐4 in an aqueous solution for 3 h using the clinically optimal 3:1 proportion of aPD1 to aCTLA‐4. PD1/CTLA‐4 BsAb significantly inhibits tumors in MC38 colon cancer‐bearing mice more effectively than the combination of aPD1 and aCTLA‐4, with tumor suppression rates of 96.8% and 77.3%, respectively. It also induces a higher percentage of CD8+ T cells and increases the secretion of effector cytokines while reducing Treg levels in tumors compared to phosphate‐buffered saline, indicating significant tumor immunity regulation. Mechanistically, a 6.3‐fold increase in PD1/CTLA‐4 BsAb accumulation in tumors due to the tumor targeting ability of aPD1, and the PD1/CTLA‐4 BsAb significantly reduces the adverse colitis event in healthy mice, compared to aPD1 and aCTLA‐4. Thus, these findings provide a novel approach to enhance antitumor therapy using aPD1 and aCTLA‐4. |
| format | Article |
| id | doaj-art-6bff3c2c0fb44506a15b0769301444ca |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-6bff3c2c0fb44506a15b0769301444ca2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202408899Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4Zongyu Liu0Hongyu Chu1Weidong Zhao2Chenguang Yang3Tongjun Liu4Na Shen5Zhaohui Tang6Department of Colorectal and Anal Surgery The Second Hospital of Jilin University Changchun Jilin 130000 ChinaDepartment of Gastrointestinal Colorectal and Anal Surgery China‐Japan Union Hospital of Jilin University Changchun Jilin 130033 ChinaKey Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 ChinaKey Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 ChinaDepartment of Colorectal and Anal Surgery The Second Hospital of Jilin University Changchun Jilin 130000 ChinaKey Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 ChinaKey Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 ChinaAbstract Dual Opdivo plus Yervoy immunotherapy, targeting the immune checkpoints PD1 and CTLA‐4, is successful in clinical use. However, it is associated with a high incidence of adverse events, and its therapeutic efficacy needs improving. In this study, polymeric multivalent Fc‐binding peptides (PLG‐Fc‐III‐4C) are employed to fabricate a bispecific antibody (PD1/CTLA‐4 BsAb) to potentiate dual immunotherapy targeting PD1 and CTLA‐4. The PD1/CTLA‐4 BsAb is prepared by mixing PLG‐Fc‐III‐4C with aPD1 and aCTLA‐4 in an aqueous solution for 3 h using the clinically optimal 3:1 proportion of aPD1 to aCTLA‐4. PD1/CTLA‐4 BsAb significantly inhibits tumors in MC38 colon cancer‐bearing mice more effectively than the combination of aPD1 and aCTLA‐4, with tumor suppression rates of 96.8% and 77.3%, respectively. It also induces a higher percentage of CD8+ T cells and increases the secretion of effector cytokines while reducing Treg levels in tumors compared to phosphate‐buffered saline, indicating significant tumor immunity regulation. Mechanistically, a 6.3‐fold increase in PD1/CTLA‐4 BsAb accumulation in tumors due to the tumor targeting ability of aPD1, and the PD1/CTLA‐4 BsAb significantly reduces the adverse colitis event in healthy mice, compared to aPD1 and aCTLA‐4. Thus, these findings provide a novel approach to enhance antitumor therapy using aPD1 and aCTLA‐4.https://doi.org/10.1002/advs.202408899CTLA‐4dual immunotherapyFc‐binding peptidePD1polymer |
| spellingShingle | Zongyu Liu Hongyu Chu Weidong Zhao Chenguang Yang Tongjun Liu Na Shen Zhaohui Tang Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4 Advanced Science CTLA‐4 dual immunotherapy Fc‐binding peptide PD1 polymer |
| title | Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4 |
| title_full | Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4 |
| title_fullStr | Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4 |
| title_full_unstemmed | Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4 |
| title_short | Polymeric Multivalent Fc Binding Peptides‐Fabricated Clinical Compounding Bispecific Antibody Potentiates Dual Immunotherapy Targeting PD1 and CTLA‐4 |
| title_sort | polymeric multivalent fc binding peptides fabricated clinical compounding bispecific antibody potentiates dual immunotherapy targeting pd1 and ctla 4 |
| topic | CTLA‐4 dual immunotherapy Fc‐binding peptide PD1 polymer |
| url | https://doi.org/10.1002/advs.202408899 |
| work_keys_str_mv | AT zongyuliu polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 AT hongyuchu polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 AT weidongzhao polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 AT chenguangyang polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 AT tongjunliu polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 AT nashen polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 AT zhaohuitang polymericmultivalentfcbindingpeptidesfabricatedclinicalcompoundingbispecificantibodypotentiatesdualimmunotherapytargetingpd1andctla4 |