Engineering a TACI×CD3 Bispecific Antibody to Redirect T Cells Against Multiple Myeloma

Engineering a TACI×CD3 Bispecific Antibody to Redirect T Cells Against Multiple Myeloma

Blood Advances

10.1182/bloodadvances.2025018210

https://doi.org/10.1182/bloodadvances.2025018210

Minchuan Zhang, Wai Fook Leong, Jianxin Huo, Eve Zi Xian Ngoh, Hanping Loh, Qingfeng Chen, Sabrina Hui Min Toh, Sanjay de Mel, Melissa GM Ooi, Cinnie Yentia Soekojo, Wee Joo Chng, Yuansheng Yang, Kong-Peng Lam, Shengli Xu

Bispecific antibody, TACI, BCMA, Multiple Myeloma, antigen escape

03 June 2026

Zhang, M., Leong, W. F., Huo, J., Ngoh, E. Z. X., Loh, H., Chen, Q., Toh, S. H. M., de Mel, S., Ooi, M. G., Soekojo, C. Y., Chng, W. J., Yang, Y., Lam, K.-P., & Xu, S. (2026). Engineering a TACI×CD3 Bispecific Antibody to Redirect T Cells Against Multiple Myeloma. Blood Advances. https://doi.org/10.1182/bloodadvances.2025018210

Immunotherapies targeting B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor (TNFR) superfamily, have demonstrated remarkable clinical efficacy in treating relapsed/refractory (RR) multiple myeloma (MM). However, a major challenge is the frequent downregulation or loss of BCMA expression in patients receiving BCMA-targeted immunotherapies, which substantially diminishes therapeutic efficacy and contributes to disease progression and treatment resistance following an initial positive response. In this study, we developed a T cell-redirecting bispecific antibody (bsAb) targeting transmembrane activator and CAML interactor (TACI), another TNFR superfamily member expressed on MM cells. The TACI × CD3 bsAb induced robust T cell activation, proliferation, and potent cytotoxicity against MM cells. Importantly, it also effectively inhibited the growth of MM cells with downregulated BCMA expression that were unresponsive to BCMA × CD3 bsAb treatment. Moreover, the TACI × CD3 bsAb mediates effect cytotoxicity against primary MM cells derived from patients. Collectively, these findings suggest that TACI-targeted T cell-redirecting bsAb may represent a promising therapeutic strategy for MM, with the potential of overcoming resistance associated with BCMA downregulation in MM.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research is supported by core funding from: Singapore Immunology Network
Grant Reference no. : N.A

© 2026 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International(CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

https://oar.a-star.edu.sg/communities-collections/articles/23261

2473-9529
2473-9537

Singapore Immunology Network

https://doi.org/10.1182/bloodadvances.2025018210