An engineered trispecific NK cell engager (TriKE) composed of anti-CD16, an IL-15 moiety, and anti-CD33 domains; designed to bridge NK cells via CD16 to induce cytotoxicity, deliver IL-15 to expand/sustain NK cells via JAK/STAT signaling, and target CD33+ leukemic blasts and myeloid-derived suppressor cells; administered as a single-agent continuous infusion in 28-day cycles.
Engineered TriKE that binds CD16 on NK cells and CD33 on target myeloid cells to form an immune synapse and trigger NK-mediated cytotoxicity; includes an IL-15 moiety to activate and expand NK cells via JAK/STAT signaling, enhancing sustained killing of CD33+ leukemic blasts and MDSCs.
NO
INDIRECT
The IL-15 moiety engages CD122 on NK cells to activate and expand them; the drug bridges NK cells (via CD16) to CD33+ targets for NK-mediated cytotoxicity. CD122-expressing cells themselves are not targeted or killed.
An engineered trispecific NK cell engager (TriKE) composed of anti-CD16, an IL-15 moiety, and anti-CD33 domains; designed to bridge NK cells via CD16 to induce cytotoxicity, deliver IL-15 to expand/sustain NK cells via JAK/STAT signaling, and target CD33+ leukemic blasts and myeloid-derived suppressor cells; administered as a single-agent continuous infusion in 28-day cycles.
Engineered TriKE that binds CD16 on NK cells and CD33 on target myeloid cells to form an immune synapse and trigger NK-mediated cytotoxicity; includes an IL-15 moiety to activate and expand NK cells via JAK/STAT signaling, enhancing sustained killing of CD33+ leukemic blasts and MDSCs.
NO
INDIRECT
The IL-15 moiety engages the IL-2/15 receptor beta/gamma (CD122/CD132) on NK cells to activate and expand them via JAK/STAT; activated NK cells then kill CD33+ targets when bridged by the anti-CD16 and anti-CD33 domains. CD132-expressing cells are not the lytic targets.
Adoptive γδ T‑cell therapy using Vγ9Vδ2 T cells expanded from healthy donors and administered intraventricularly/intracavitary via an Ommaya reservoir. These innate‑like cytotoxic lymphocytes recognize tumor phosphoantigens via BTN3A1/BTN2A1 independent of MHC, triggering perforin/granzyme‑mediated killing and cytokine release; they can also respond via NKG2D and mediate ADCC.
Allogeneic Vγ9Vδ2 T cells recognize tumor-derived phosphoantigens generated by dysregulated mevalonate metabolism via BTN3A1/BTN2A1 in an MHC-independent manner, triggering perforin/granzyme-mediated cytotoxicity and cytokine release. They also respond to stress ligands through NKG2D and can mediate ADCC.
YES
DIRECT
Vγ9Vδ2 T cells express NKG2D that binds MICA on target cells, activating an immune synapse and inducing perforin/granzyme-mediated apoptosis (with supportive cytokine release).
An anti-HER2 antibody-drug conjugate (RC48-ADC) in which a humanized anti-HER2 monoclonal antibody delivers the microtubule-disrupting payload monomethyl auristatin E (MMAE) via a cleavable linker; after HER2 binding and internalization, MMAE is released to induce G2/M arrest and apoptosis, with possible bystander effect and Fc-mediated ADCC.
Humanized anti‑HER2 monoclonal antibody binds HER2 on tumor cells, is internalized, and a cleavable linker releases MMAE, which binds tubulin to inhibit microtubule polymerization, causing G2/M arrest and apoptosis; may exert a bystander effect and engage Fc-mediated ADCC.
YES
DIRECT
Anti-HER2 ADC binds HER2, is internalized, and releases MMAE via a cleavable linker; MMAE inhibits microtubule polymerization leading to G2/M arrest and apoptosis (with possible Fc-mediated ADCC and bystander effect).
An anti-HER2 antibody-drug conjugate (RC48-ADC) in which a humanized anti-HER2 monoclonal antibody delivers the microtubule-disrupting payload monomethyl auristatin E (MMAE) via a cleavable linker; after HER2 binding and internalization, MMAE is released to induce G2/M arrest and apoptosis, with possible bystander effect and Fc-mediated ADCC.
Humanized anti‑HER2 monoclonal antibody binds HER2 on tumor cells, is internalized, and a cleavable linker releases MMAE, which binds tubulin to inhibit microtubule polymerization, causing G2/M arrest and apoptosis; may exert a bystander effect and engage Fc-mediated ADCC.
NO
INDIRECT
The ADC binds HER2 on tumor cells, is internalized, and releases MMAE, which binds tubulin to inhibit microtubule polymerization, causing G2/M arrest and apoptosis (with possible bystander effect and Fc-mediated ADCC). Tubulin itself is not the antigen targeted by the drug.