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- Title
A Novel T Cell-Engaging Bispecific Antibody for Treating Mesothelin-Positive Solid Tumors.
- Authors
Yoon, Aerin; Lee, Shinai; Lee, Sua; Lim, Sojung; Park, Yong-Yea; Song, Eunjung; Kim, Dong-Sik; Kim, Kisu; Lim, Yangmi
- Abstract
As mesothelin is overexpressed in various types of cancer, it is an attractive target for therapeutic antibodies. T-cell bispecific antibodies bind to target cells and engage T cells via binding to CD3, resulting in target cell killing by T-cell activation. However, the affinity of the CD3-binding arm may influence CD3-mediated plasma clearance or antibody trapping in T-cell-containing tissues. This may then affect the biodistribution of bispecific antibodies. In this study, we used scFab and knob-into-hole technologies to construct novel IgG-based 1 + 1 MG1122-A and 2 + 1 MG1122-B bispecific antibodies against mesothelin and CD3ε. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3ε, using a 2 + 1 head-to-tail format. Activities of the two antibodies were evaluated in mesothelin-positive tumor cells in vitro and xenograft models in vivo. Although both antibodies exhibited target cell killing efficacy and produced regression of xenograft tumors with CD8+ T-cell infiltration, the antitumor efficacy of MG1122-B was significantly higher. MG1122-B may improve tumor targeting because of its bivalency for tumor antigen. It may also reduce systemic toxicity by limiting the activation of circulating T cells. Thus, MG1122-B may be useful for treating mesothelin-positive solid tumors.
- Subjects
BISPECIFIC antibodies; TUMOR antigens; TUMORS; IMMUNOGLOBULINS
- Publication
Biomolecules (2218-273X), 2020, Vol 10, Issue 3, p399
- ISSN
2218-273X
- Publication type
Article
- DOI
10.3390/biom10030399