A HER2-targeted antibody–drug conjugate composed of trastuzumab linked via a cleavable linker to the topoisomerase I inhibitor payload deruxtecan (DXd); binds HER2 (ERBB2), is internalized, and releases DXd to inhibit topo I and induce DNA damage/apoptosis, with potential bystander effect and Fc-mediated ADCC.
HER2-targeted ADC: trastuzumab binds HER2 (ERBB2), is internalized, and via a cleavable linker releases the topoisomerase I inhibitor deruxtecan (DXd) in lysosomes, causing DNA damage and apoptosis; the membrane-permeable payload enables a bystander effect, and the antibody Fc can mediate ADCC.
YES
DIRECT
The ADC binds HER2 on target cells, is internalized, and releases the deruxtecan topoisomerase I inhibitor via a cleavable linker, causing DNA damage and apoptosis; the antibody Fc can also mediate ADCC, with potential bystander killing from the membrane-permeable payload.
A HER2-targeted antibody–drug conjugate composed of trastuzumab linked via a cleavable linker to the topoisomerase I inhibitor payload deruxtecan (DXd); binds HER2 (ERBB2), is internalized, and releases DXd to inhibit topo I and induce DNA damage/apoptosis, with potential bystander effect and Fc-mediated ADCC.
HER2-targeted ADC: trastuzumab binds HER2 (ERBB2), is internalized, and via a cleavable linker releases the topoisomerase I inhibitor deruxtecan (DXd) in lysosomes, causing DNA damage and apoptosis; the membrane-permeable payload enables a bystander effect, and the antibody Fc can mediate ADCC.
NO
INDIRECT
T-DXd binds HER2, is internalized, and releases DXd that inhibits topoisomerase I to cause DNA damage and apoptosis; topoisomerase I is not the targeting antigen, so its expression alone does not make cells directly killed by the drug.
Autologous engineered T-cell therapy with a logic-gate circuit to recognize PSMA and CA9; CAR-like activation enabling targeted cytotoxicity against clear-cell renal cell carcinoma. Administered as a single IV infusion; designed to enhance tumor specificity and reduce off-tumor toxicity.
Autologous T cells engineered with a PSMA-inducible anti-CA9 CAR (logic-gate circuit). Engagement of PSMA triggers expression of an anti-CA9 CAR, enabling CAR-like activation and cytotoxic killing of PSMA/CA9-expressing tumor cells. Embedded shRNA-miR modules downregulate Fas and TGFβRII to resist apoptosis and TGF-β–mediated immunosuppression, and a constitutive activator enhances STAT3 signaling to promote T-cell expansion and function, improving specificity and reducing off-tumor toxicity.
NO
INDIRECT
PSMA serves as a priming signal; its engagement induces expression of an anti‑CA9 CAR. Killing is mediated by the CA9 CAR (T‑cell cytotoxicity via perforin/granzyme) against CA9+ cells, not by PSMA recognition itself.
Autologous engineered T-cell therapy with a logic-gate circuit to recognize PSMA and CA9; CAR-like activation enabling targeted cytotoxicity against clear-cell renal cell carcinoma. Administered as a single IV infusion; designed to enhance tumor specificity and reduce off-tumor toxicity.
Autologous T cells engineered with a PSMA-inducible anti-CA9 CAR (logic-gate circuit). Engagement of PSMA triggers expression of an anti-CA9 CAR, enabling CAR-like activation and cytotoxic killing of PSMA/CA9-expressing tumor cells. Embedded shRNA-miR modules downregulate Fas and TGFβRII to resist apoptosis and TGF-β–mediated immunosuppression, and a constitutive activator enhances STAT3 signaling to promote T-cell expansion and function, improving specificity and reducing off-tumor toxicity.
YES
DIRECT
PSMA engagement induces anti-CA9 CAR expression; the CAR T cells then recognize CA9 on tumor cells and directly lyse them via T-cell cytotoxic pathways (perforin/granzyme, death-receptor signaling).