Fresh donor-derived, second-generation CD19-directed CAR T cells (lentiviral-transduced) that express a CAR with CD3ζ and a costimulatory domain to recognize CD19 on B cells, leading to T-cell activation, proliferation, cytotoxic killing of CD19+ cells, and expected B-cell aplasia.
Allogeneic, lentiviral-transduced T cells engineered with a second-generation anti-CD19 CAR (CD3z plus a costimulatory domain) recognize CD19 on B cells, leading to T-cell activation, proliferation, and cytotoxic killing of CD19+ cells, with expected on-target B-cell aplasia.
YES
DIRECT
Anti-CD19 CAR T cells recognize CD19 via the CAR and directly kill CD19+ cells through T-cell effector mechanisms (perforin/granzyme and Fas–FasL), leading to on-target B-cell aplasia.
Anti-CD20 monoclonal antibody that depletes B cells via ADCC, CDC, and apoptosis.
Anti-CD20 chimeric monoclonal IgG1 that binds CD20 on pre-B and mature B cells and depletes them via Fc-mediated antibody-dependent cellular cytotoxicity and phagocytosis, complement-dependent cytotoxicity, and direct induction of apoptosis.
YES
DIRECT
Anti-CD20 antibody binds CD20 on B cells and triggers Fc-mediated ADCC and phagocytosis, complement-dependent cytotoxicity, and can induce apoptosis of the target cells.
Autologous, gene-edited CD19-directed CAR T-cell therapy with a CD28 costimulatory domain and a 1XX ITAM-modulated CD3ζ chain; the CAR is inserted into the TRAC locus to knock out the endogenous TCR, standardize CAR expression, and reduce tonic signaling/GvHD risk; designed to eliminate CD19+ malignant B cells and enhance persistence while limiting exhaustion.
Autologous T cells are gene-edited to insert a CD19-targeted CAR with CD28 costimulation and a 1XX-modified CD3zeta activation domain into the TRAC locus, knocking out the endogenous TCR. Upon infusion, the cells bind CD19 on B cells, trigger CAR-mediated activation and cytotoxicity, and eliminate malignant B cells. TRAC integration reduces tonic signaling and GvHD risk and standardizes CAR expression, while the 1XX ITAM design tempers signaling to limit exhaustion and improve persistence.
YES
DIRECT
Anti-CD19 CAR T cells bind CD19 on target cells and induce T cell–mediated killing via perforin/granzyme release and death receptor–mediated apoptosis.
An anti-CD19 IgG1 antibody–drug conjugate that binds CD19 on B cells, is internalized, and releases a pyrrolobenzodiazepine (PBD) dimer cytotoxic payload that forms DNA interstrand crosslinks leading to apoptosis; Fc-mediated effector functions may contribute.
Anti-CD19 IgG1 antibody–drug conjugate that binds CD19 on B cells, is internalized, and releases a pyrrolobenzodiazepine (PBD) dimer payload via a cleavable linker; the PBD binds DNA minor grooves to form interstrand crosslinks, blocking DNA replication and inducing apoptosis; Fc-mediated effector functions may also contribute.
YES
DIRECT
Anti-CD19 ADC binds CD19, is internalized, and releases a PBD dimer that crosslinks DNA, blocking replication and inducing apoptosis; Fc-mediated effector functions may also contribute.
An anti-CD19 IgG1 antibody–drug conjugate that binds CD19 on B cells, is internalized, and releases a pyrrolobenzodiazepine (PBD) dimer cytotoxic payload that forms DNA interstrand crosslinks leading to apoptosis; Fc-mediated effector functions may contribute.
Anti-CD19 IgG1 antibody–drug conjugate that binds CD19 on B cells, is internalized, and releases a pyrrolobenzodiazepine (PBD) dimer payload via a cleavable linker; the PBD binds DNA minor grooves to form interstrand crosslinks, blocking DNA replication and inducing apoptosis; Fc-mediated effector functions may also contribute.
NO
INDIRECT
Loncastuximab tesirine targets CD19 on B cells; after internalization, its PBD payload binds the DNA minor groove (N2 of guanines) to form interstrand crosslinks and trigger apoptosis. DNA is the intracellular payload target, not the selective cell-surface target.