Development of a tetravalent anti-GPA33/anti-CD3 bispecific antibody for colorectal cancers Journal Article
| Authors: | Wu, Z.; Guo, H. F.; Xu, H.; Cheung, N. K. V. |
| Article Title: | Development of a tetravalent anti-GPA33/anti-CD3 bispecific antibody for colorectal cancers |
| Abstract: | Despite progress in the treatment of colorectal cancer, curing metastatic colorectal cancer remains a major unmet medical need worldwide. Here, we describe a T-cell-engaging bispecific antibody (T-BsAb) to redirect polyclonal cytotoxic T cells to eradicate colorectal cancer. A33, a murine antibody specific for GPA33, was humanized to huA33 and reformatted to huA33-BsAb, based on a novel IgG(L)-scFv platform by linking the anti-CD3 huOKT3 scFv to the carboxyl end of the light chain. This T-BsAb was stably expressed in CHO cells and purified as a stable monomer by HPLC, retaining immunoreactivity by FACS through 30 days of incubation at 37C. In vitro, it induced activation and expansion of unstimulated T cells and elicited potent T-cell-dependent cell-mediated cytotoxicity against colon and gastric cancer cells in an antigen-specific manner. In vivo, huA33-BsAb inhibited the colon and gastric cancer xenografts, in both subcutaneous and intraperitoneal tumor models. More importantly, both microsatellite instable and microsatellite stable colorectal cancer were effectively eliminated by huA33-BsAb. These preclinical results provide further support for the use of IgG(L)-scFv platform to build BsAb, and especially one targeting GPA33 for colorectal cancer. These preclinical results also support further development of huA33-BsAb as a potential immunotherapeutic. © 2018 American Association for Cancer Research. |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 17 |
| Issue: | 10 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2018-10-01 |
| Start Page: | 2164 |
| End Page: | 2175 |
| Language: | English |
| DOI: | 10.1158/1535-7163.mct-18-0026 |
| PUBMED: | 30082472 |
| PROVIDER: | scopus |
| PMCID: | PMC6168351 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 November 2018 -- Source: Scopus |
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