Development of a T cell-redirecting bispecific antibody targeting B-cell maturation antigen for the suppression of multiple myeloma cell growth

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Development of a T cell-redirecting bispecific antibody targeting B-cell maturation antigen for the suppression of multiple myeloma cell growth
Title:
Development of a T cell-redirecting bispecific antibody targeting B-cell maturation antigen for the suppression of multiple myeloma cell growth
Journal Title:
Antibody Therapeutics
Publication Date:
09 June 2022
Citation:
Huo, J., Huang, Y., Zheng, Z., Tay, X. N., Mahfut, F. B., Zhang, W., Lam, K.-P., Yang, Y., & Xu, S. (2022). Development of a T cell-redirecting bispecific antibody targeting B-cell maturation antigen for the suppression of multiple myeloma cell growth. Antibody Therapeutics, 5(2), 138–149. https://doi.org/10.1093/abt/tbac012
Abstract:
Multiple myeloma (MM) is the second most common hematological malignancy. It has emerged as one of the next possible hematological diseases amenable to immunotherapy. B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily, is highly expressed in MM cells and is one target with the most potential for developing MM-targeting immunotherapy. Other than the FDA-approved BCMA-targeting CAR T-cell therapy, such as Abecma and CARVYKTI, T cell-engaging multi-specific antibody is another promising therapeutic modality for BCMA-targeting MM treatment. We develop a T-cell redirecting BCMA-targeting bispecific antibody (bsAb) and evaluate its anti-MM activity.MethodsWe first generated several clones of mouse anti-human BCMA monoclonal antibodies using DNA immunization. One of the anti-BCMA antibodies was then used to design and produce a T cell-redirecting BCMA × CD3 bsAb in CHO cells. Finally, we examined the effect of the bsAb on MM cell growth both in vitro and in vivo.ResultsThe BCMA × CD3 bsAb was designed in a FabscFv format and produced in CHO cells with good yield and purity. Moreover, the bsAb can trigger robust T cell proliferation and activation and induce efficient T cell-mediated MM cell killing in vitro. Using a MM xenograft mouse model, we demonstrate that the bsAb can effectively suppress MM cell growth in vivo.ConclusionsOur results suggest that the BCMA × CD3 bsAb in the FabscFv format can efficiently inhibit MM cell growth and have promising potential to be developed into a therapeutic antibody drug for the treatment of MM.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research is supported by core funding from: Singapore Agency for Science Technology and Research.
Grant Reference no. : NA
Description:
ISSN:
2516-4236