Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies
T-cell-engaging bispecific antibodies (T-bsAbs) are promising immunotherapies for cancer treatment due to their capability of redirecting T-cells toward destroying tumor cells. Numerous T-bsAb formats have been developed, each with advantages and disadvantages in terms of developability, immunogenic...
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| 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/10.1080/19420862.2023.2231129 |
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| author | Han Ping Loh Farouq Bin Mahfut Serene W Chen Yuhan Huang Jianxin Huo Wei Zhang Kong Peng Lam Shengli Xu Yuansheng Yang |
| author_facet | Han Ping Loh Farouq Bin Mahfut Serene W Chen Yuhan Huang Jianxin Huo Wei Zhang Kong Peng Lam Shengli Xu Yuansheng Yang |
| author_sort | Han Ping Loh |
| collection | DOAJ |
| description | T-cell-engaging bispecific antibodies (T-bsAbs) are promising immunotherapies for cancer treatment due to their capability of redirecting T-cells toward destroying tumor cells. Numerous T-bsAb formats have been developed, each with advantages and disadvantages in terms of developability, immunogenicity, effector functions, and pharmacokinetics. Here, we systematically compared T-bsAbs produced using eight different formats, evaluating the effect of molecular design of T-bsAbs on their manufacturability and functionality. These eight T-bsAb formats were constructed using antigen-binding fragments (Fabs) and single-chain variable fragments (scFvs) of antibodies linked to the crystallizable fragment (Fc) domain of immunoglobulin G. To ensure a fair comparison of growth and production data, we used recombinase-mediated cassette exchange technology to generate the T-bsAb-producing CHO cell lines. The produced T-bsAbs were assessed for their purification profile and recovery, binding capability, and biological activities. Our findings indicated that the manufacturability of bsAbs was adversely affected with increased number of scFv building blocks, while the functionality was affected by the combination of multiple factors, including the binding affinity and avidity of targeting moieties and the flexibility and geometry of formats. These results provide valuable insights into the impact of the format design on the optimal production and function of T-bsAbs. |
| format | Article |
| id | doaj-art-8d90c44d609a46ee84e4e146feab623d |
| institution | DOAJ |
| issn | 1942-0862 1942-0870 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | mAbs |
| spelling | doaj-art-8d90c44d609a46ee84e4e146feab623d2025-08-20T02:50:29ZengTaylor & Francis GroupmAbs1942-08621942-08702023-12-0115110.1080/19420862.2023.2231129Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodiesHan Ping Loh0Farouq Bin Mahfut1Serene W Chen2Yuhan Huang3Jianxin Huo4Wei Zhang5Kong Peng Lam6Shengli Xu7Yuansheng Yang8Bioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeBioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeBioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Immunology Network (SIGN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Immunology Network (SIGN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeBioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Immunology Network (SIGN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeSingapore Immunology Network (SIGN), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeBioprocessing Technology Institute (BTI), Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeT-cell-engaging bispecific antibodies (T-bsAbs) are promising immunotherapies for cancer treatment due to their capability of redirecting T-cells toward destroying tumor cells. Numerous T-bsAb formats have been developed, each with advantages and disadvantages in terms of developability, immunogenicity, effector functions, and pharmacokinetics. Here, we systematically compared T-bsAbs produced using eight different formats, evaluating the effect of molecular design of T-bsAbs on their manufacturability and functionality. These eight T-bsAb formats were constructed using antigen-binding fragments (Fabs) and single-chain variable fragments (scFvs) of antibodies linked to the crystallizable fragment (Fc) domain of immunoglobulin G. To ensure a fair comparison of growth and production data, we used recombinase-mediated cassette exchange technology to generate the T-bsAb-producing CHO cell lines. The produced T-bsAbs were assessed for their purification profile and recovery, binding capability, and biological activities. Our findings indicated that the manufacturability of bsAbs was adversely affected with increased number of scFv building blocks, while the functionality was affected by the combination of multiple factors, including the binding affinity and avidity of targeting moieties and the flexibility and geometry of formats. These results provide valuable insights into the impact of the format design on the optimal production and function of T-bsAbs.https://www.tandfonline.com/doi/10.1080/19420862.2023.2231129CHO cellaviditybispecific antibodyfunctionalitymanufacturabilitytargeted integration |
| spellingShingle | Han Ping Loh Farouq Bin Mahfut Serene W Chen Yuhan Huang Jianxin Huo Wei Zhang Kong Peng Lam Shengli Xu Yuansheng Yang Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies mAbs CHO cell avidity bispecific antibody functionality manufacturability targeted integration |
| title | Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies |
| title_full | Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies |
| title_fullStr | Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies |
| title_full_unstemmed | Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies |
| title_short | Manufacturability and functionality assessment of different formats of T-cell engaging bispecific antibodies |
| title_sort | manufacturability and functionality assessment of different formats of t cell engaging bispecific antibodies |
| topic | CHO cell avidity bispecific antibody functionality manufacturability targeted integration |
| url | https://www.tandfonline.com/doi/10.1080/19420862.2023.2231129 |
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