CD138-targeted bispecific protein engager-armed T cells exhibit potent and selective cytotoxicity against multiple myeloma cells
Issued Date
2026-04-01
Resource Type
ISSN
15675769
eISSN
18781705
Scopus ID
2-s2.0-105031150801
Pubmed ID
41687522
Journal Title
International Immunopharmacology
Volume
174
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Immunopharmacology Vol.174 (2026)
Suggested Citation
Songprakhon P., Luangwattananun P., Choomee K., Sawasdee N., Somboonpatarakun C., Chieochansin T., Sukpanichnant S., Junking M., Okada S., Yenchitsomanus P.T. CD138-targeted bispecific protein engager-armed T cells exhibit potent and selective cytotoxicity against multiple myeloma cells. International Immunopharmacology Vol.174 (2026). doi:10.1016/j.intimp.2026.116295 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115526
Title
CD138-targeted bispecific protein engager-armed T cells exhibit potent and selective cytotoxicity against multiple myeloma cells
Author's Affiliation
Corresponding Author(s)
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Abstract
Multiple myeloma (MM) is a hematologic malignancy that remains incurable, with most patients eventually relapsing or developing resistance to available therapies. Bispecific T cell engagers (BiTEs) have shown promise by redirecting T cells to target and kill tumor cells; however, their clinical application is hindered by a short in vivo half-life, the need for high dosing, and treatment-related toxicities. To address these limitations, bispecific protein engager-armed T cells (BATs) have been developed as a novel cell-based immunotherapy platform that enhances antigen specificity and in vivo persistence. In this study, we evaluated the antitumor efficacy of BATs targeting CD138, a heparan sulfate proteoglycan highly expressed on MM cells and associated with disease progression. BATs were generated by arming T cells with an anti-CD138 × anti-CD3 bispecific protein engager (BiPE), and their antitumor activity was assessed through counting bead technique and flow cytometry. CD138-specific BATs exhibited potent cytotoxicity against CD138-positive MM.1R cells, achieving up to 89.62 ± 2.22% cell lysis after 48 h of co-culture, significantly surpassing the activity of unarmed T cells (33.04 ± 6.57% lysis). Additionally, BATs induced robust expression of interleukin-2 (IL-2) cytokine and cytolytic mediators, including perforin, granzyme A/B, soluble Fas ligand (sFasL), and TNF-α, indicating effective antigen-specific activation. Importantly, pro-inflammatory cytokines such as IL-6, IL-10, and IFN-γ remained at low levels, suggesting a favorable safety profile. These findings support the therapeutic potential of CD138-targeted BATs as a promising and potentially safer cellular immunotherapy for the treatment of MM.