Rovalpituzumab tesirine (SC-002) is an antibody-drug conjugate (ADC) with anticancer properties. It consists of the DLL3-targeting antibody, Rovalpituzumab, which is linked to a cytotoxic pyrrolobenzodiazepine compound via a protease-cleavable linker. Rovalpituzumab tesirine is utilized in research concerning small cell lung cancer (SCLC).

Rovalpituzumab tesirine (0.01-10000 pM, 96 h) effectively binds to murine DLL3 in KP1 cells (a model for small cell lung cancer, SCLC) and exhibits potent cytotoxic effects by internalizing the PBD toxin.

Rovalpituzumab tesirine, administered intraperitoneally at doses of 0.03, 0.1, and 0.3 mg/kg, exhibits a dose-dependent inhibition of tumor growth in SCLC mouse models. Complete remission is achieved at 0.3 mg/kg, and its antitumor efficacy is enhanced when combined with anti-PD1 therapy. When given at 0.03 mg/kg once every four days, this combination increases CD8+ T cell infiltration and activation within the tumor, upregulates PD-L1 and MHC1 expressions, overcomes immune suppression, and activates the DC and STING pathways for a synergistic antitumor effect. Furthermore, combination with anti-PD1 at a dose of 0.1 mg/kg confirms CD8+ T cells as crucial effector cells for efficacy, while administration of 0.03 mg/kg induces long-term antitumor immune memory when combined with anti-PD1.