Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity
ABSTRACTClinical studies have shown that combination therapy of antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) significantly improves clinical benefit over PD-1 antibody alone. However, broad application of this combination has been limited by toxic...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | mAbs |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19420862.2023.2180794 |
| _version_ | 1797356267307532288 |
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| author | Xinghua Pang Zhaoliang Huang Tingting Zhong Peng Zhang Zhongmin Maxwell Wang Michelle Xia Baiyong Li |
| author_facet | Xinghua Pang Zhaoliang Huang Tingting Zhong Peng Zhang Zhongmin Maxwell Wang Michelle Xia Baiyong Li |
| author_sort | Xinghua Pang |
| collection | DOAJ |
| description | ABSTRACTClinical studies have shown that combination therapy of antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) significantly improves clinical benefit over PD-1 antibody alone. However, broad application of this combination has been limited by toxicities. Cadonilimab (AK104) is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possess higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy. |
| first_indexed | 2024-03-08T14:24:08Z |
| format | Article |
| id | doaj.art-625306aac51d4b8385dd9cd69cb468e1 |
| institution | Directory Open Access Journal |
| issn | 1942-0862 1942-0870 |
| language | English |
| last_indexed | 2024-03-08T14:24:08Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj.art-625306aac51d4b8385dd9cd69cb468e12024-01-13T11:27:52ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2180794Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidityXinghua Pang0Zhaoliang Huang1Tingting Zhong2Peng Zhang3Zhongmin Maxwell Wang4Michelle Xia5Baiyong Li6Research and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaResearch and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaResearch and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaResearch and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaResearch and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaResearch and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaResearch and Development Department, Akeso Biopharma, Inc, Zhongshan, ChinaABSTRACTClinical studies have shown that combination therapy of antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) significantly improves clinical benefit over PD-1 antibody alone. However, broad application of this combination has been limited by toxicities. Cadonilimab (AK104) is a symmetric tetravalent bispecific antibody with a crystallizable fragment (Fc)-null design. In addition to demonstrating biological activity similar to that of the combination of CTLA-4 and PD-1 antibodies, cadonilimab possess higher binding avidity in a high-density PD-1 and CTLA-4 setting than in a low-density PD-1 setting, while a mono-specific anti-PD-1 antibody does not demonstrate this differential activity. With no binding to Fc receptors, cadonilimab shows minimal antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and interleukin-6 (IL-6)/IL-8 release. These features all likely contribute to significantly lower toxicities of cadonilimab observed in the clinic. Higher binding avidity of cadonilimab in a tumor-like setting and Fc-null design may lead to better drug retention in tumors and contribute to better safety while achieving anti-tumor efficacy.https://www.tandfonline.com/doi/10.1080/19420862.2023.2180794PD-1/CTLA-4 bispecific antibodydrug retentiontumor microenvironment |
| spellingShingle | Xinghua Pang Zhaoliang Huang Tingting Zhong Peng Zhang Zhongmin Maxwell Wang Michelle Xia Baiyong Li Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity mAbs PD-1/CTLA-4 bispecific antibody drug retention tumor microenvironment |
| title | Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity |
| title_full | Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity |
| title_fullStr | Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity |
| title_full_unstemmed | Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity |
| title_short | Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity |
| title_sort | cadonilimab a tetravalent pd 1 ctla 4 bispecific antibody with trans binding and enhanced target binding avidity |
| topic | PD-1/CTLA-4 bispecific antibody drug retention tumor microenvironment |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2180794 |
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