An intravenous anti-HER2 antibody–drug conjugate (trastuzumab linked via a cleavable linker to the topoisomerase I inhibitor payload deruxtecan [DXd]); binds HER2 (including HER2-low), internalizes, and releases DXd to inhibit topoisomerase I causing DNA damage and apoptosis; retains trastuzumab-mediated HER2 blockade and ADCC with bystander killing.
Anti-HER2 antibody–drug conjugate: trastuzumab targets HER2 (including HER2-low), is internalized, and releases the topoisomerase I–inhibiting payload deruxtecan (DXd), causing DNA damage, cell-cycle arrest, and apoptosis. Retains trastuzumab-mediated HER2 blockade and Fc-dependent ADCC, with a membrane-permeable payload enabling bystander killing.
YES
DIRECT
The anti-HER2 ADC binds HER2, is internalized, and releases the topoisomerase I inhibitor DXd, causing DNA damage and apoptosis; it also engages Fc-mediated ADCC and can cause bystander killing.
An intravenous anti-HER2 antibody–drug conjugate (trastuzumab linked via a cleavable linker to the topoisomerase I inhibitor payload deruxtecan [DXd]); binds HER2 (including HER2-low), internalizes, and releases DXd to inhibit topoisomerase I causing DNA damage and apoptosis; retains trastuzumab-mediated HER2 blockade and ADCC with bystander killing.
Anti-HER2 antibody–drug conjugate: trastuzumab targets HER2 (including HER2-low), is internalized, and releases the topoisomerase I–inhibiting payload deruxtecan (DXd), causing DNA damage, cell-cycle arrest, and apoptosis. Retains trastuzumab-mediated HER2 blockade and Fc-dependent ADCC, with a membrane-permeable payload enabling bystander killing.
YES
INDIRECT
After HER2 binding and internalization (or via bystander diffusion), the ADC releases deruxtecan, which inhibits topoisomerase I in the cell, causing DNA damage, cell‑cycle arrest, and apoptosis. Top1 is not the antibody-recognized target, but the intracellular enzymatic target of the payload.
Non-replicating, off-the-shelf gene therapy vector that delivers HSV-enhanced thymidine kinase (suicide gene) and human GM-CSF to tumors, making transduced cells susceptible to valganciclovir and enhancing antitumor immune activation via myeloid APC recruitment.
Non-replicating gene therapy vector that transduces tumor cells to express HSV-enhanced thymidine kinase and human GM-CSF. After vector delivery, oral valganciclovir is phosphorylated by HSV-tk in transduced cells to ganciclovir triphosphate, which inhibits DNA synthesis and kills those tumor cells. Resultant antigen release plus locally expressed GM-CSF recruits and activates myeloid antigen-presenting cells, enhances antigen presentation, and promotes cytotoxic T-cell (and NK)–mediated antitumor immunity.
NO
INDIRECT
GM-CSF from the vector activates GM-CSF receptor–expressing myeloid cells; they are not killed. Killing occurs in HSV-tk–transduced tumor cells after valganciclovir is converted to ganciclovir triphosphate (DNA synthesis inhibition) and via subsequent T/NK-cell–mediated tumor killing.
Non-replicating, off-the-shelf gene therapy vector that delivers HSV-enhanced thymidine kinase (suicide gene) and human GM-CSF to tumors, making transduced cells susceptible to valganciclovir and enhancing antitumor immune activation via myeloid APC recruitment.
Non-replicating gene therapy vector that transduces tumor cells to express HSV-enhanced thymidine kinase and human GM-CSF. After vector delivery, oral valganciclovir is phosphorylated by HSV-tk in transduced cells to ganciclovir triphosphate, which inhibits DNA synthesis and kills those tumor cells. Resultant antigen release plus locally expressed GM-CSF recruits and activates myeloid antigen-presenting cells, enhances antigen presentation, and promotes cytotoxic T-cell (and NK)–mediated antitumor immunity.
NO
INDIRECT
GEN2 kills HSV‑tk–transduced tumor cells after valganciclovir is converted to ganciclovir triphosphate, inhibiting DNA synthesis. GM‑CSF activates/recruits myeloid APCs via the GM‑CSF receptor; those receptor‑expressing cells are not targeted for killing.
Non-replicating, off-the-shelf gene therapy vector that delivers HSV-enhanced thymidine kinase (suicide gene) and human GM-CSF to tumors, making transduced cells susceptible to valganciclovir and enhancing antitumor immune activation via myeloid APC recruitment.
Non-replicating gene therapy vector that transduces tumor cells to express HSV-enhanced thymidine kinase and human GM-CSF. After vector delivery, oral valganciclovir is phosphorylated by HSV-tk in transduced cells to ganciclovir triphosphate, which inhibits DNA synthesis and kills those tumor cells. Resultant antigen release plus locally expressed GM-CSF recruits and activates myeloid antigen-presenting cells, enhances antigen presentation, and promotes cytotoxic T-cell (and NK)–mediated antitumor immunity.
YES
DIRECT
Tumor cells transduced to express HSV‑enhanced thymidine kinase phosphorylate valganciclovir/ganciclovir to ganciclovir triphosphate, which inhibits DNA synthesis (DNA polymerase/chain elongation), causing death of those transduced cells.