Journal
BIOMOLECULES
Volume 10, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/biom10030399
Keywords
mesothelin; CD3; bispecific antibody; solid tumor; cancer immunotherapy; T cell-engaging; heterodimeric bivalent; heterodimeric trivalent; tumor regression
Categories
Funding
- Mogam Institute for Biomedical Research and GC Pharma, Republic of Korea
Ask authors/readers for more resources
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 CD3 epsilon. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3 epsilon, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available