An antibody–drug conjugate comprising a humanized anti–Trop-2 IgG linked to SN-38 (active metabolite of irinotecan), delivering a topoisomerase I inhibitor to Trop-2–expressing tumor cells to induce DNA damage and apoptosis.
Humanized anti–Trop-2 IgG linked to SN-38 (active irinotecan metabolite). The antibody binds Trop-2 on tumor cells, is internalized, and releases SN-38 after cleavage. SN-38 inhibits topoisomerase I by stabilizing Topo I–DNA complexes, causing DNA strand breaks, blocking replication, and inducing apoptosis, with potential bystander cytotoxicity.
NO
INDIRECT
The ADC binds Trop-2 (not TOP1), is internalized, and releases SN-38, which inhibits topoisomerase I to cause DNA damage and apoptosis. TOP1 is the intracellular enzymatic target of the payload, not the targeted antigen; any killing of TOP1-expressing cells occurs only after Trop-2–mediated delivery (with possible bystander effect).
Autologous anti-CD4 chimeric antigen receptor T-cell therapy: patient T cells are lentivirally transduced to express an anti-CD4 scFv (derived from humanized mAb ibalizumab) linked to a third-generation CAR with CD28 and 4-1BB co-stimulatory domains and a CD3ζ activation domain; administered as a single IV dose after lymphodepleting chemotherapy to target and eliminate CD4+ leukemic blasts.
Autologous T cells are lentivirally transduced to express an anti-CD4 scFv-based third-generation CAR (CD28 and 4-1BB costimulatory domains with CD3zeta signaling). After lymphodepletion and IV infusion, the CAR T cells bind CD4 on leukemic blasts, triggering activation, expansion, cytokine release, and perforin/granzyme-mediated cytotoxic killing of CD4+ cells. Expected on-target effect includes depletion of normal CD4 T cells (T-cell aplasia).
YES
DIRECT
Anti-CD4 CAR T cells bind CD4 on target cells, become activated, and kill via perforin/granzyme-mediated cytolysis (and possibly Fas–FasL apoptosis), leading to depletion of CD4+ cells.
Autologous, genetically engineered TCR-T cell therapy expressing an HLA-A*11:01–restricted T cell receptor specific for the KRAS G12D neoantigen; administered after lymphodepletion with a single IV infusion to recognize KRAS G12D peptides on tumor HLA-A*11:01, expand (with low-dose IL-2 support), and mediate cytotoxic killing of tumor cells in advanced solid tumors.
Autologous T cells are engineered to express an HLA-A*11:01–restricted TCR that recognizes the KRAS G12D neoantigen. Following lymphodepletion and IV infusion (with low-dose IL-2 support), the cells bind KRAS G12D peptides presented on tumor HLA-A*11:01, activate, expand, and mediate MHC-restricted cytotoxic killing of tumor cells.
YES
DIRECT
Engineered TCR-T cells recognize KRAS G12D peptide presented by HLA-A*11:01 on tumor cells and directly induce cytotoxic T-lymphocyte killing (perforin/granzyme-mediated apoptosis, Fas–FasL).
Half-life–extended bispecific T-cell engager (BiTE) antibody biologic that binds BCMA on malignant plasma cells and CD3 on T cells to redirect and activate cytotoxic T cells against BCMA-positive multiple myeloma cells; administered subcutaneously (± IV).
Half-life–extended bispecific T-cell engager antibody that binds BCMA on malignant plasma cells and CD3 on T cells, creating an immune synapse to redirect and activate cytotoxic T cells, leading to targeted lysis of BCMA-positive myeloma cells.
YES
DIRECT
AMG 701 bridges CD3 on T cells to BCMA on target cells, forming an immune synapse and activating T cells to kill BCMA+ cells via perforin/granzyme-mediated cytolysis.
Half-life–extended bispecific T-cell engager (BiTE) antibody biologic that binds BCMA on malignant plasma cells and CD3 on T cells to redirect and activate cytotoxic T cells against BCMA-positive multiple myeloma cells; administered subcutaneously (± IV).
Half-life–extended bispecific T-cell engager antibody that binds BCMA on malignant plasma cells and CD3 on T cells, creating an immune synapse to redirect and activate cytotoxic T cells, leading to targeted lysis of BCMA-positive myeloma cells.
NO
INDIRECT
AMG 701 binds CD3 on T cells to recruit and activate them; the T cells then kill BCMA-positive tumor cells (perforin/granzyme). CD3+ T cells themselves are not targeted for lysis.