Antitumor activity of T cells secreting αCD133- αCD3 bispecific T-cell engager against cholangiocarcinoma
Issued Date
2022-03-01
Resource Type
eISSN
19326203
Scopus ID
2-s2.0-85126868357
Pubmed ID
35312724
Journal Title
PLoS ONE
Volume
17
Issue
3 March
Rights Holder(s)
SCOPUS
Bibliographic Citation
PLoS ONE Vol.17 No.3 March (2022)
Suggested Citation
Sangsuwannukul T., Supimon K., Chieochansin T., Choomee K., Sujjitjoon J., Junking M., Yenchitsomanus P. Antitumor activity of T cells secreting αCD133- αCD3 bispecific T-cell engager against cholangiocarcinoma. PLoS ONE Vol.17 No.3 March (2022). doi:10.1371/journal.pone.0265773 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86596
Title
Antitumor activity of T cells secreting αCD133- αCD3 bispecific T-cell engager against cholangiocarcinoma
Author's Affiliation
Other Contributor(s)
Abstract
Cholangiocarcinoma (CCA) is a lethal cancer of bile duct epithelial cells with a high mortality rate and limited therapeutic options. An effective treatment is, therefore, urgently needed to improve treatment outcomes for these patients. To develop a new therapeutic option, we engineered T cells secreting αCD133-αCD3 bispecific T-cell engager and evaluated their antitumor effects against CD133-expressing CCA cells. The cDNA encoding αCD133- αCD3 bispecific T-cell engager (αCD133-αCD3-ENG) was cloned into pCDH lentiviral construct and its expression was tested in Lenti-X 293T cells. T cells from healthy donors were then transduced with engineered lentiviruses to create T cells secreting αCD133-αCD3 engager to evaluate their antitumor activities. The average transduction efficiency into T cells was approximately 60.03±21.65%. In the co-culture system containing T cells secreting αCD133-αCD3 engager (as effector cells) and mWasabi-luciferase-expressing CCA cells (KKU-100 and KKU-213A; as target cells), the effector T cells exhibited significantly higher cytolytic activities against the target CCA cells (49.0±9.76% and 64.10±13.18%, respectively) than those observed against the untransduced T cells (10.97±10.65%; p = 0.0103 and 9.80±11.05%; p = 0.0054) at an effector-to-target ratio of 5:1. In addition, the secreted αCD133-αCD3 engager significantly redirected both transduced T cells and bystander T cells to kill the target CCA cells (up to 73.20±1.68%; p<0.05). Moreover, the transduced and bystander T cells could kill the target CCA spheroids at a rate approximately 5-fold higher than that of the no treatment control condition (p = 0.0011). Our findings demonstrate proof-of-principle that T cells secreting αCD133-αCD3 engager can be an alternative approach to treating CD133-positive CCA, and they pave the way for future in vivo study and clinical trials.