Description

Whole IgG-like Bispecific T-cell Engaging Antibody for Breast Cancer Immunotherapy

Munkyung Kim, Kisu Kim, Okjae Lim, Duckhyang Shin, Hyojung Nam, Yunjung Lee, Hyeji Choi, Junhong Jung, Haenaem Kwon, Jaewhan Ryu, Yangmi Lim, Hyungkwon Lim, Jonghwa Won

MOGAM Institute for Biomedical Research, 93, 30beon-gil, Ihyeon-ro, Giheung-gu, Youngin-si, Gyeonggi-do, South Korea

Immunotherapy with tumor antigen specific T-cell engagers is actively being pursued for its therapeutic applications in solid cancers. We generated (scFab)₂-Fc format, whole IgG-like, bispecific antibody targeting CD3 and breast cancer specific antigen ‘A’ (A/CD3-bispecific antibody) and evaluated its therapeutic potential. Our data showed that A/CD3-bispecific antibody induced activation of NFAT-RE-luc2 Jurkat T cells co-cultivated with A⁺ breast cancer cells in a dose-dependent manner. A⁺ breast cancer cells were killed by A/CD3-bispecific antibody dose-dependently, when incubated with human PBMCs at an E:T ratio of 5:1. This cytotoxicity was accompanied by activation of CD4 and CD8 cells in human PBMCs, as shown by upregulation of activation markers, CD25 and CD69, and increased secretion of granzyme B, IFN-γ, IL-2 and TNF. In conclusion, our A/CD3-bispecific antibody offers a promising opportunity to redirect immune effector cells to kill A⁺ breast cancer cells.