Invariant NKT cells dictate antitumor immunity elicited by a bispecific antibody cotargeting CD3 and BCMA
- Author(s)
- Casey, M; Tu, C; Harrison, SJ; Nakamura, K;
- Details
- Publication Year 2022-09-13,Volume 6,Issue #17,Page 5165-5170
- Journal Title
- Blood Advances
- Publication Type
- Research article
- Abstract
- CD3-engaging bispecific antibodies (BsAbs) have emerged as powerful therapeutic approaches by their ability to redirect T cells to eliminate tumor cells in a major histocompatibility complex-independent manner. However, how we can potentiate the efficacy of BsAbs remains largely unknown. To address this question, we investigated immunological mechanisms of action of a BsAb cotargeting CD3 and B-cell maturation antigen (BCMA) in syngeneic preclinical myeloma models. Treatment with the CD3/BCMA BsAb stimulated multiple CD3-expressing T-cell subsets and natural killer (NK) cells in the myeloma bone marrow (BM), highlighting its broad immunostimulatory effect. Notably, the BsAb-mediated immunostimulatory and antitumor effects were abrogated in mice lacking invariant NKT (iNKT) cells. Mechanistically, activation of iNKT cells and interleukin-12 production from dendritic cells (DCs) were crucial upstream events for triggering effective antitumor immunity by the BsAb. Myeloma progression was associated with a reduced number of BM iNKT cells. Importantly, the therapeutic efficacy of a single dose of CD3/BCMA BsAb was remarkably augmented by restoring iNKT cell activity, using adoptive transfer of alpha-galactosylceramide-loaded DCs. Together, these results reveal iNKT cells as critical players in the antitumor activity of CD3 engaging BsAbs and have important translational implications.
- Keywords
- Animals; *Antibodies, Bispecific/pharmacology/therapeutic use; B-Cell Maturation Antigen/therapeutic use; CD3 Complex; Mice; *Multiple Myeloma/drug therapy; *Natural Killer T-Cells
- Department(s)
- Clinical Haematology
- PubMed ID
- 35830292
- Publisher's Version
- https://doi.org/10.1182/bloodadvances.2022008118
- Open Access at Publisher's Site
https://doi.org/10.1182/bloodadvances.2022008118- Terms of Use/Rights Notice
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Creation Date: 2024-10-11 06:53:07
Last Modified: 2024-10-11 06:58:07