Small-molecule antiviral prodrug of ganciclovir; in this study it is phosphorylated by HSV-eTK expressed from GEN2 to induce selective tumor cell death.
Valganciclovir is a prodrug of ganciclovir (a deoxyguanosine analogue). After phosphorylation by HSV-enhanced thymidine kinase (expressed by the GEN2 vector) and subsequent cellular kinases, the active triphosphate is incorporated into DNA, inhibiting DNA polymerase and causing DNA chain termination, leading to selective death of transduced tumor cells.
YES
DIRECT
HSV-1 thymidine kinase in expressing cells phosphorylates valganciclovir (ganciclovir), which is further converted to the triphosphate that is incorporated into DNA, inhibits DNA polymerase, and causes chain termination, killing the expressing cells.
An intravenous antibody–drug conjugate (ADC) composed of an anti–Nectin-4 monoclonal antibody that binds Nectin-4 (PVRL4) on tumor cells, is internalized, and releases an intracellular cytotoxic payload to kill Nectin-4–expressing cells, with potential bystander effect.
LY4101174 is an intravenous anti–Nectin-4 IgG1 antibody–drug conjugate that binds Nectin-4 (PVRL4) on tumor cells, is internalized, and releases the topoisomerase I inhibitor exatecan via a cleavable linker, causing inhibition of DNA replication, cell‑cycle arrest, and apoptosis of Nectin‑4–expressing cells, with potential bystander effect.
YES
DIRECT
The ADC binds Nectin-4 on target cells, is internalized, and releases the topoisomerase I inhibitor exatecan via a cleavable linker, inhibiting DNA replication and inducing cell-cycle arrest and apoptosis (with potential bystander effect).
Small-molecule antiviral prodrug of ganciclovir; in this study it is phosphorylated by HSV-eTK expressed from GEN2 to induce selective tumor cell death.
Valganciclovir is a prodrug of ganciclovir (a deoxyguanosine analogue). After phosphorylation by HSV-enhanced thymidine kinase (expressed by the GEN2 vector) and subsequent cellular kinases, the active triphosphate is incorporated into DNA, inhibiting DNA polymerase and causing DNA chain termination, leading to selective death of transduced tumor cells.
NO
INDIRECT
Valganciclovir is activated by HSV-thymidine kinase (from the GEN2 vector) to ganciclovir triphosphate, which is incorporated into DNA and inhibits DNA polymerases, causing chain termination and death of HSV-TK–transduced cells. Expression of DNA polymerase alpha alone does not confer selective killing by this drug.
Small-molecule antiviral prodrug of ganciclovir; in this study it is phosphorylated by HSV-eTK expressed from GEN2 to induce selective tumor cell death.
Valganciclovir is a prodrug of ganciclovir (a deoxyguanosine analogue). After phosphorylation by HSV-enhanced thymidine kinase (expressed by the GEN2 vector) and subsequent cellular kinases, the active triphosphate is incorporated into DNA, inhibiting DNA polymerase and causing DNA chain termination, leading to selective death of transduced tumor cells.
NO
INDIRECT
Valganciclovir is activated by HSV-thymidine kinase in transduced cells; the resulting ganciclovir triphosphate is incorporated by cellular DNA polymerases, causing chain termination and death. Killing depends on HSV-TK expression, not on DNA polymerase delta expression.
Small-molecule antiviral prodrug of ganciclovir; in this study it is phosphorylated by HSV-eTK expressed from GEN2 to induce selective tumor cell death.
Valganciclovir is a prodrug of ganciclovir (a deoxyguanosine analogue). After phosphorylation by HSV-enhanced thymidine kinase (expressed by the GEN2 vector) and subsequent cellular kinases, the active triphosphate is incorporated into DNA, inhibiting DNA polymerase and causing DNA chain termination, leading to selective death of transduced tumor cells.
NO
INDIRECT
Valganciclovir must be phosphorylated by HSV-thymidine kinase from the GEN2 vector; active ganciclovir triphosphate is incorporated into DNA and inhibits DNA polymerases, causing chain termination and killing HSV‑TK–transduced tumor cells, not cells merely expressing DNA polymerase epsilon.