An autologous NKG2D-based CAR T-cell therapy in which patient T cells are gene-engineered to express a chimeric antigen receptor using the NKG2D receptor ectodomain fused to intracellular activation/costimulatory domains (e.g., CD3ζ). The cells target stress-induced NKG2D ligands (MICA, MICB, ULBP1–6) on tumor cells to mediate cytotoxicity and cytokine release.
Autologous T cells are engineered to express an NKG2D-based CAR (NKG2D ectodomain fused to 4-1BB and CD3ζ signaling domains) that recognizes stress-induced NKG2D ligands (MICA, MICB, ULBP1–6) on tumors, activating T cells to release cytokines and mediate perforin/granzyme-dependent cytotoxicity against NKG2DL-positive cancer cells.
YES
DIRECT
NKG2D-CAR T cells bind ULBP2 on target cells, become activated via 4-1BB/CD3ζ signaling, and kill the bound cells through perforin/granzyme-mediated cytotoxicity with cytokine release.
An antibody–drug conjugate (ADC) consisting of a humanized anti-HER2 IgG1 (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). It binds HER2, is internalized, and releases DXd in lysosomes to cause topoisomerase I–mediated DNA damage and tumor cell death; also inhibits HER2 signaling and can induce Fc-mediated ADCC with potential bystander killing.
An anti-HER2 monoclonal antibody (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). After HER2 binding and internalization, lysosomal cleavage releases DXd, which inhibits topoisomerase I, causing DNA damage, cell cycle arrest, and apoptosis; the antibody also inhibits HER2 signaling, can trigger Fc-mediated ADCC, and supports bystander killing.
NO
INDIRECT
The ADC binds HER2, is internalized, and releases DXd, which inhibits topoisomerase I to cause DNA damage and apoptosis. Killing depends on HER2-mediated delivery (with possible bystander effect), not on expression of topoisomerase I itself.
Ex vivo–expanded, patient-derived T cells recognizing tumor neoantigens via TCRs; administered via hepatic arterial infusion to kill melanoma cells through perforin/granzyme and cytokine release and establish durable anti-tumor immunity.
Autologous, ex vivo-expanded tumor-infiltrating T cells that recognize patient-specific tumor neoantigens via native TCRs; after hepatic arterial infusion they home to liver metastases and kill melanoma cells through perforin/granzyme-mediated cytolysis and cytokine release, with expansion/persistence to provide durable anti-tumor immunity.
YES
DIRECT
Transferred TILs recognize the patient-specific neoantigen peptide–HLA class I complex via their native TCRs and directly kill the presenting cells through perforin/granzyme-mediated cytolysis (and Fas–FasL/apoptotic pathways).
Ex vivo–expanded, patient-derived T cells recognizing tumor neoantigens via TCRs; administered via hepatic arterial infusion to kill melanoma cells through perforin/granzyme and cytokine release and establish durable anti-tumor immunity.
Autologous, ex vivo-expanded tumor-infiltrating T cells that recognize patient-specific tumor neoantigens via native TCRs; after hepatic arterial infusion they home to liver metastases and kill melanoma cells through perforin/granzyme-mediated cytolysis and cytokine release, with expansion/persistence to provide durable anti-tumor immunity.
YES
DIRECT
TILs recognizing the neoantigen–HLA class II complex via their native TCRs directly kill target-expressing tumor cells through perforin/granzyme cytolysis and can also trigger apoptosis via death receptor signaling and proinflammatory cytokines.
Anti-CD38 IgG1 monoclonal antibody that depletes CD38+ plasma cells/plasmablasts via ADCC/CDC/apoptosis and inhibits CD38 ectoenzyme activity to reduce donor-specific antibody production.
Isatuximab is a humanized IgG1 anti-CD38 monoclonal antibody that binds CD38 on plasma cells/plasmablasts and other CD38+ cells, inducing antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and apoptosis; it also inhibits CD38 ectoenzyme activity, resulting in depletion of CD38+ cells and reduced pathogenic antibody production.
YES
DIRECT
Isatuximab binds CD38 on target cells and triggers Fc-mediated ADCC and complement-dependent cytotoxicity, and can directly induce apoptosis, leading to killing of CD38+ cells.