HER2-targeted antibody–drug conjugate composed of a humanized anti-HER2 IgG1 (disitamab) linked via a cleavable linker to the cytotoxic payload MMAE. After binding ERBB2 (HER2) on tumor cells and internalization, MMAE is released to inhibit tubulin polymerization, causing G2/M arrest and apoptosis; the Fc region may mediate ADCC and bystander killing.
Disitamab vedotin targets HER2 (ERBB2) on tumor cells; after binding and internalization, its cleavable linker releases the microtubule poison MMAE, which inhibits tubulin polymerization causing G2/M arrest and apoptosis. The IgG1 Fc may also mediate ADCC and enable bystander killing.
NO
INDIRECT
RC48-ADC targets HER2, not β-tubulin. After HER2-mediated internalization, MMAE is released and inhibits β-tubulin to block microtubule polymerization, causing G2/M arrest and apoptosis; Fc-mediated ADCC and bystander effects may contribute.
Potent microtubule inhibitor (auristatin class) serving as the cytotoxic payload in the RC48-ADC; disrupts tubulin polymerization leading to mitotic arrest and apoptosis. In this trial it is delivered only via the disitamab vedotin conjugate, not as free drug.
Monomethyl auristatin E (MMAE) is an auristatin microtubule inhibitor that binds tubulin and blocks polymerization, inducing G2/M mitotic arrest and apoptosis. In this trial it is released intracellularly as the cytotoxic payload of the HER2-targeted ADC disitamab vedotin (RC48), enabling targeted killing of HER2-expressing tumor cells with potential bystander effect.
NO
INDIRECT
The ADC (disitamab vedotin) targets HER2, is internalized, and releases MMAE, which binds beta-tubulin (vinca site) to block microtubule polymerization, causing G2/M arrest and apoptosis. Killing is driven by HER2-directed delivery (with possible bystander effect), not by tubulin expression per se.
Human IgG1 monoclonal antibody immune-checkpoint inhibitor targeting PD-L1; blocks PD-L1/PD-1 signaling to restore anti-tumor T-cell activity and can mediate Fc-dependent ADCC against PD-L1–positive tumor cells.
Avelumab is a human IgG1 monoclonal antibody that binds PD-L1, blocking its interaction with PD-1 to release inhibitory signaling on T cells and restore anti-tumor immunity; its intact Fc can also mediate antibody-dependent cellular cytotoxicity (ADCC) against PD-L1–expressing tumor cells.
YES
DIRECT
Avelumab binds PD-L1 and, via its IgG1 Fc, engages FcγR-bearing effector cells (e.g., NK cells) to mediate ADCC against PD-L1–expressing cells; PD-1/PD-L1 blockade also restores T-cell killing.
Anti-HER2 monoclonal antibody that inhibits HER2/ERBB2 signaling and mediates antibody-dependent cellular cytotoxicity in HER2-positive tumor cells.
Humanized anti-HER2 (ERBB2) IgG1 monoclonal antibody that binds HER2 on tumor cells, inhibits HER2 signaling and proliferation, and induces antibody-dependent cellular cytotoxicity (ADCC) against HER2-overexpressing cells.
YES
DIRECT
Trastuzumab binds HER2 on target cells and its Fc engages Fcγ receptors on effector cells (e.g., NK cells), triggering ADCC and lysis of HER2-positive cells.
Engineered allogeneic cord blood–derived natural killer cells expressing an HLA-A*02:01–restricted T-cell receptor specific for PRAME to enable antigen-specific recognition and cytotoxic killing of PRAME-positive myeloid blasts.
Allogeneic cord blood-derived NK cells engineered to express an HLA-A*02:01-restricted T-cell receptor specific for PRAME. The TCR recognizes PRAME peptide-HLA-A*02:01 complexes on tumor cells, leading to antigen-specific NK activation and cytotoxic lysis (perforin/granzyme) of PRAME-positive myeloid blasts.
NO
INDIRECT
Engineered NK cells kill only cells presenting PRAME peptide in HLA-A*02:01 via TCR engagement, triggering perforin/granzyme-mediated lysis; HLA-A*02:01 alone is not sufficient.