Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma
Abstrak
Abstract Chimeric Antigen Receptor (CAR) T cells directed to B cell maturation antigen (BCMA) mediate profound responses in patients with multiple myeloma, but most patients do not achieve long-term complete remissions. In addition, recent evidence suggests that high-affinity binding to BCMA can result in on-target, off-tumor activity in the basal ganglia and can lead to fatal Parkinsonian-like disease. Here we develop CAR T cells against multiple myeloma using a binder to targeting transmembrane activator and CAML interactor (TACI) in mono and dual-specific formats with anti-BCMA. These CARs have robust, antigen-specific activity in vitro and in vivo. We also show that TACI RNA expression is limited in the basal ganglia, which may circumvent some of the toxicities recently reported with BCMA CARs. Thus, single-targeting TACI CARs may have a safer toxicity profile, whereas dual-specific BCMA-TACI CAR T cells have potential to avoid the antigen escape that can occur with single-antigen targeting.
Topik & Kata Kunci
Penulis (15)
Rebecca C. Larson
Michael C. Kann
Charlotte Graham
Christopher W. Mount
Ana P. Castano
Won-Ho Lee
Amanda A. Bouffard
Hana N. Takei
Antonio J. Almazan
Irene Scarfó
Trisha R. Berger
Andrea Schmidts
Matthew J. Frigault
Kathleen M. E. Gallagher
Marcela V. Maus
Akses Cepat
- Tahun Terbit
- 2023
- Sumber Database
- DOAJ
- DOI
- 10.1038/s41467-023-43416-7
- Akses
- Open Access ✓