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**LV-169-BCMA-CAR** is an intravenously administered, CD3-targeted lentiviral gene-therapy candidate designed to generate anti-BCMA CAR-T cells directly in vivo for the treatment of multiple myeloma. The LV-169 vector uses LDL receptor-blinded vesicular stomatitis virus glycoprotein envelopes displaying an anti-CD3 single-chain variable fragment to selectively bind, activate, and transduce resting T cells in lymphoid tissues. It delivers a fully human anti-BCMA single-heavy-chain nanobody CAR incorporating 4-1BB and CD3 zeta signaling domains; the CAR cassette is driven by a T-cell-specific Lck promoter in reverse orientation to minimize CAR protein incorporation into vector particles and reduce off-target transduction of BCMA-positive myeloma cells. In humanized mouse models of disseminated OPM-2 multiple myeloma, a single intravenous administration eliminated tumors and generated circulating CAR-T cells with limited cytokine release.
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