An intravenous CD19-directed, T-cell–redirecting biologic immunotherapy given with step-up dosing; binds CD19 on B cells to engage and activate T cells for cytotoxic killing of malignant B cells, with expected on-target depletion of normal CD19+ B cells. Studied in CD19+ B-cell malignancies (B-NHL, B-ALL, CLL).
A trispecific T-cell engager antibody that binds CD19 on B cells and CD3/CD28 on T cells to crosslink and costimulate T cells, redirecting cytotoxic activity against CD19+ malignant B cells; on-target depletion of normal CD19+ B cells is expected.
NO
INDIRECT
CD3 is on T cells and is engaged (with CD28) to activate and redirect T cells to kill CD19+ B cells via immune synapse formation and perforin/granzyme release; CD3+ cells are not the cytotoxic targets.
An intravenous CD19-directed, T-cell–redirecting biologic immunotherapy given with step-up dosing; binds CD19 on B cells to engage and activate T cells for cytotoxic killing of malignant B cells, with expected on-target depletion of normal CD19+ B cells. Studied in CD19+ B-cell malignancies (B-NHL, B-ALL, CLL).
A trispecific T-cell engager antibody that binds CD19 on B cells and CD3/CD28 on T cells to crosslink and costimulate T cells, redirecting cytotoxic activity against CD19+ malignant B cells; on-target depletion of normal CD19+ B cells is expected.
NO
INDIRECT
CC312 binds CD28 (and CD3) on T cells to costimulate and engage them to kill CD19+ B cells; CD28+ T cells are not targeted for cytotoxic killing and are activated rather than killed.
Patient-derived T lymphocytes genetically engineered to express a chimeric antigen receptor targeting B-cell antigens (e.g., CD19) for MHC-independent recognition and killing of malignant B cells via CD3ζ and costimulatory domains (CD28 or 4-1BB); associated immune activation can lead to CRS and ICANS.
Autologous T cells are genetically engineered to express a chimeric antigen receptor (e.g., anti-CD19) that recognizes B-cell antigens independently of MHC and signals via CD3zeta with CD28 or 4-1BB costimulation, activating cytotoxicity and cytokine release to eliminate malignant B cells (with risks of CRS and ICANS).
YES
DIRECT
CAR-T cells recognize CD19 via the CAR and, upon activation (CD3ζ with costimulation), directly kill CD19+ cells through perforin/granzyme release and death-receptor pathways.
iPSC-derived natural killer cells engineered with dual chimeric antigen receptors targeting CD33 and CLL1 (CLEC12A) to recognize AML blasts and mediate NK cytotoxicity.
iPSC-derived natural killer cells engineered with dual chimeric antigen receptors against CD33 and CLL1 (CLEC12A) bind these antigens on AML blasts, triggering NK-cell activation and targeted cytotoxicity (perforin/granzyme release and cytokine-mediated killing) to eliminate leukemia cells and reduce antigen escape.
YES
DIRECT
CAR-engineered NK cells bind CD33 on target cells, activating NK cytotoxicity and killing via perforin/granzyme-mediated lysis/apoptosis.
iPSC-derived natural killer cells engineered with dual chimeric antigen receptors targeting CD33 and CLL1 (CLEC12A) to recognize AML blasts and mediate NK cytotoxicity.
iPSC-derived natural killer cells engineered with dual chimeric antigen receptors against CD33 and CLL1 (CLEC12A) bind these antigens on AML blasts, triggering NK-cell activation and targeted cytotoxicity (perforin/granzyme release and cytokine-mediated killing) to eliminate leukemia cells and reduce antigen escape.
YES
DIRECT
CAR-NK cells bind CLL1 (CLEC12A) on target cells, triggering NK activation and degranulation (perforin/granzyme) leading to apoptotic/lytic killing, with additional cytokine-mediated cytotoxicity.