HLX43

HLX43 is a PD-L1-targeting antibody-drug conjugate (ADC). The antibody component is the anti-PD-L1 antibody Opucolimab (T77120), which is conjugated to the camptothecin-derived topoisomerase I inhibitor payload C24 through a tumor microenvironment-activatable tripeptide linker, with a drug-to-antibody ratio (DAR) of 8. HLX43 can block the PD-1/PD-L1 interaction and release the payload through protease-mediated linker cleavage in the tumor microenvironment, enabling both intracellular payload release after tumor cell internalization and extracellular bystander killing effects. HLX43 can be used for research in tumor immunology, ADC drug delivery, and tumor microenvironment-responsive therapeutic strategies^[1][2].

Method: HLX43 or the free payload C24 was tested in NCI-H1975, NCI-H292, NCI-H441, and NCI-H226 NSCLC cells at the indicated concentration gradients for 96 h, followed by cell viability measurement using the CTG assay.
Result: The IC₅₀ values of HLX43 in NCI-H1975, NCI-H292, NCI-H441, and NCI-H226 cells were 235.7, 144.7, 28.2, and 166.4 nM, respectively, while the IC₅₀ values of C24 were 5.09, 6.30, 1.34, and 4.04 nM, respectively, indicating that HLX43 exhibits cytotoxicity across NSCLC cells with different PD-L1 expression levels, with NCI-H441 cells being the most sensitive to HLX43^[1].
Method: PD-L1-overexpressing HEK293T cells were treated with HLX43, C24, HLX20, or corresponding controls at the indicated concentration gradients for 96 h, followed by cell viability assessment.
Result: HLX43 showed enhanced tumor cell killing activity in PD-L1-overexpressing cells, whereas the parental antibody HLX20 showed minimal direct cytotoxicity, suggesting that HLX43-mediated cytotoxicity is mainly associated with payload delivery^[1].

Method: In a PD-L1-positive squamous NSCLC PDX model (PD-L1 IHC 2+), HLX43 was administered at 1, 3, or 8 mg/kg once weekly for three doses (QW×3). Control groups included isotype ADC at 8 mg/kg and HLX20 at 8 mg/kg, both QW×3.
Result: HLX43 showed dose-dependent antitumor activity in this model, with a TGI of 92.7% on day 21 at 8 mg/kg, outperforming HLX20 and isotype ADC^[1].
Method: In an anti-PD-1 antibody- and chemotherapy-resistant colorectal cancer PDX model (PD-L1 IHC 3+, TPS 100%), HLX43 was administered at 10 mg/kg once weekly for four doses (QW×4). Control groups included vehicle, C24 at 0.24 mg/kg QW×4, and HLX20 at 10 mg/kg QW×4.
Result: HLX43 at 10 mg/kg showed significant antitumor activity, with a TGI of 101.6% on day 31, and demonstrated stronger activity than free C24 and the parental antibody HLX20^[1].

Human

Antibody: Opucolimab (T77120)
Linker: Cleavable linker
Payload: Camptothecin-based toxin