Metelimumab

NIS793 is a human IgG2 monoclonal antibody that binds to transforming growth factor beta (TGF-β). This first-in-human study investigated NIS793 plus spartalizumab treatment in patients with advanced solid tumors.

Patients received NIS793 (0.3–1 mg/kg every 3 weeks (Q3W)) monotherapy; following evaluation of two dose levels, dose escalation continued with NIS793 plus spartalizumab (NIS793 0.3–30 mg/kg Q3W and spartalizumab 300 mg Q3W or NIS793 20–30 mg/kg every 2 weeks [Q2W] and spartalizumab 400 mg every 4 weeks (Q4W)). In dose expansion, patients with non-small cell lung cancer (NSCLC) resistant to prior anti-programmed death ligand 1 or patients with microsatellite stable colorectal cancer (MSS-CRC) were treated at the recommended dose for expansion (RDE).

Sixty patients were treated in dose escalation, 11 with NIS793 monotherapy and 49 with NIS793 plus spartalizumab, and 60 patients were treated in dose expansion (MSS-CRC: n=40; NSCLC: n=20). No dose-limiting toxicities were observed. The RDE was established as NIS793 30 mg/kg (2100 mg) and spartalizumab 300 mg Q3W. Overall 54 (49.5%) patients experienced ≥1 treatment-related adverse event, most commonly rash (n=16; 13.3%), pruritus (n=10; 8.3%), and fatigue (n=9; 7.5%). Three partial responses were reported: one in renal cell carcinoma (NIS793 30 mg/kg Q2W plus spartalizumab 400 mg Q4W), and two in the MSS-CRC expansion cohort. Biomarker data showed evidence of target engagement through increased TGF-β/NIS793 complexes and depleted active TGF-β in peripheral blood. Gene expression analyses in tumor biopsies demonstrated decreased TGF-β target genes and signatures and increased immune signatures.

In patients with advanced solid tumors, proof of mechanism of NIS793 is supported by evidence of target engagement and TGF-β pathway inhibition.

NCT02947165.

In this study, acetylated soda lignin (ASL) and non-acetylated soda lignin (SL) were extruded with PLA in different concentrations to fabricate antioxidant polylactic acid (PLA)/lignin composites for potential biomedical applications. After lignin acetylation, good compatibility was observed between PLA and lignin in scanning electron microscopy images. All the PLA/ASL composites displayed higher mechanical properties than PLA/SL composites. PLA/ASL5 displayed the highest mechanical characteristics with elongation at break of 10% and tensile strength of 57 MPa, while PLA/SL15 and PLA/SL20 demonstrated superior UV-blocking potential with UV transmittance less than 10%. Addition of ASL in PLA lead to an increase in the hydrophobic character, with all the PLA/ASL displaying a higher water contact angle. The antioxidant test using 2,2-diphenyl-1-picrylhydrazyl assay showed that PLA/SL composites rendered superior radical scavenging activity (RSA), with PLA/SL20 composites displaying an RSA of 80%. Furthermore, in vitro antioxidant activity and cytocompatibility were analyzed using human colon cancer cells (HCT-15) and gastric epithelial cells (NCC-24). In vitro antioxidant activity, evaluated by H₂O₂ exposure was confirmed by a live/dead assay. PLA/SL composites protected both types of cells from oxidative stress. In addition, all PLA/SL and PLA/ASL composites promoted cell proliferation compared to PLA. PLA/SL5 and PLA/SL10 displayed the highest cell proliferation of all composites. Lastly, all PLA/SL and PLA/ASL composites had a hemoglobin release less than 2%. The antioxidant properties, cytocompatibility, and hemocompatibility of lignin/PLA demonstrated in our study indicate that these lignin/PLA composites possess the desirable attributes for potential biomedical applications.