Fourth-generation autologous gene-modified T cells expressing chimeric antigen receptors that co-target BCMA and CD19; administered as a single intravenous infusion (0.5–3 × 10^6 cells/kg) following lymphodepletion to deplete B-lineage cells in refractory autoimmune diseases.
Autologous, gene‑modified T cells engineered with chimeric antigen receptors that co-target CD19 on B cells and BCMA on plasmablasts/plasma cells. Antigen engagement triggers CAR signaling to activate T‑cell cytotoxicity and cytokine release, leading to depletion of B‑lineage cells and reduction of autoreactive B cells and autoantibody‑producing plasma cells.
YES
DIRECT
CAR-T cells recognize CD19 via the CAR and directly kill CD19+ cells through perforin/granzyme-mediated cytolysis and apoptosis.
A TROP2-targeted antibody–drug conjugate (SKB264/MK-2870) composed of a humanized anti-TROP2 monoclonal antibody linked to a camptothecin-class topoisomerase I inhibitor payload. After binding TROP2 on urothelial carcinoma cells and internalization, it releases the payload to inhibit topoisomerase I, causing DNA single-strand breaks, replication stress, S-phase arrest, and apoptosis; a bystander effect may occur. Administered intravesically in this trial.
Humanized anti‑TROP2 IgG1 ADC that binds TROP2 on tumor cells, is internalized, and releases the camptothecin‑class topoisomerase I inhibitor tirumotecan via cleavable linker, causing topoisomerase I inhibition, DNA single‑strand breaks, S‑phase arrest, and apoptosis, with a potential bystander effect.
NO
INDIRECT
The ADC binds TROP2 on tumor cells, is internalized, and releases the tirumotecan payload, which inhibits topoisomerase I to cause DNA damage and apoptosis; killing is driven by TROP2 targeting (with possible bystander effect), not by topoisomerase I expression alone.
Fourth-generation autologous gene-modified T cells expressing chimeric antigen receptors that co-target BCMA and CD19; administered as a single intravenous infusion (0.5–3 × 10^6 cells/kg) following lymphodepletion to deplete B-lineage cells in refractory autoimmune diseases.
Autologous, gene‑modified T cells engineered with chimeric antigen receptors that co-target CD19 on B cells and BCMA on plasmablasts/plasma cells. Antigen engagement triggers CAR signaling to activate T‑cell cytotoxicity and cytokine release, leading to depletion of B‑lineage cells and reduction of autoreactive B cells and autoantibody‑producing plasma cells.
YES
DIRECT
BCMA+ cells are recognized by the anti-BCMA CAR on infused T cells, which upon engagement activate cytotoxic effector functions (perforin/granzyme and Fas/FasL), causing apoptosis/lysis of BCMA-expressing plasmablasts/plasma cells.
A subcutaneous GPRC5D×CD3 bispecific T‑cell–engaging monoclonal antibody that redirects T cells to kill malignant plasma cells in multiple myeloma.
Humanized CD3×GPRC5D bispecific antibody that binds CD3 on T cells and GPRC5D on malignant plasma cells, crosslinking them to form an immune synapse, activate TCR/CD3 signaling and cytokine release, and drive cytotoxic T‑cell–mediated killing of GPRC5D‑expressing myeloma cells (with limited expression on normal tissues).
YES
DIRECT
Talquetamab links CD3 on T cells to GPRC5D on target cells, forming an immune synapse and activating T-cell cytotoxicity (perforin/granzyme, Fas–FasL) to kill GPRC5D-expressing cells.
A subcutaneous GPRC5D×CD3 bispecific T‑cell–engaging monoclonal antibody that redirects T cells to kill malignant plasma cells in multiple myeloma.
Humanized CD3×GPRC5D bispecific antibody that binds CD3 on T cells and GPRC5D on malignant plasma cells, crosslinking them to form an immune synapse, activate TCR/CD3 signaling and cytokine release, and drive cytotoxic T‑cell–mediated killing of GPRC5D‑expressing myeloma cells (with limited expression on normal tissues).
NO
INDIRECT
Talquetamab binds CD3 on T cells to recruit and activate them; the activated T cells then kill GPRC5D-expressing tumor cells via immune synapse formation and perforin/granzyme-mediated cytotoxicity, not the CD3+ cells.