Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. The authors developed ciltacabtagene autoleucel (cilta-cel) for treating multiple myeloma. Small-angle X-ray scattering method was used to characterize interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. The results provide a framework for contemplating the AIM approach in designing next-generation CARs.
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