Bispecific T cell engager-armed T cells targeting integrin ανβ6 exhibit enhanced T cell redirection and antitumor activity in cholangiocarcinoma
Issued Date
2024-06-01
Resource Type
ISSN
07533322
eISSN
19506007
Scopus ID
2-s2.0-85192507188
Journal Title
Biomedicine and Pharmacotherapy
Volume
175
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomedicine and Pharmacotherapy Vol.175 (2024)
Suggested Citation
Suwanchiwasiri K., Phanthaphol N., Somboonpatarakun C., Yuti P., Sujjitjoon J., Luangwattananun P., Maher J., Yenchitsomanus P., Junking M. Bispecific T cell engager-armed T cells targeting integrin ανβ6 exhibit enhanced T cell redirection and antitumor activity in cholangiocarcinoma. Biomedicine and Pharmacotherapy Vol.175 (2024). doi:10.1016/j.biopha.2024.116718 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98353
Title
Bispecific T cell engager-armed T cells targeting integrin ανβ6 exhibit enhanced T cell redirection and antitumor activity in cholangiocarcinoma
Corresponding Author(s)
Other Contributor(s)
Abstract
Advanced cholangiocarcinoma (CCA) presents a clinical challenge due to limited treatment options, necessitating exploration of innovative therapeutic approaches. Bispecific T cell engager (BTE)-armed T cell therapy shows promise in hematological and solid malignancies, offering potential advantages in safety over continuous BTE infusion. In this context, we developed a novel BTE, targeting CD3 on T cells and integrin αvβ6, an antigen elevated in various epithelial malignancies, on cancer cells. The novel BTE was generated by fusing an integrin αvβ6-binding peptide (A20) to an anti-CD3 (OKT3) single-chain variable fragment (scFv) through a G4S peptide linker (A20/αCD3 BTE). T cells were then armed with A20/αCD3 BTE (A20/αCD3-armed T cells) and assessed for antitumor activity. Our results highlight the specific binding of A20/αCD3 BTE to CD3 on T cells and integrin αvβ6 on target cells, effectively redirecting T cells towards these targets. After co-culture, A20/αCD3-armed T cells exhibited significantly heightened cytotoxicity against integrin αvβ6-expressing target cells compared to unarmed T cells in both KKU-213A cells and A375.β6 cells. Moreover, in a five-day co-culture, A20/αCD3-armed T cells demonstrated superior cytotoxicity against KKU-213A spheroids compared to unarmed T cells. Importantly, A20/αCD3-armed T cells exhibited an increased proportion of the effector memory T cell (Tem) subset, upregulation of T cell activation markers, enhanced T cell proliferation, and increased cytolytic molecule/cytokine production, when compared to unarmed T cells in an integrin αvβ6-dependent manner. These findings support the potential of A20/αCD3-armed T cells as a novel therapeutic approach for integrin αvβ6-expressing cancers.