Envafolimab

Transarterial chemoembolization (TACE) remains a cornerstone locoregional therapy for hepatocellular carcinoma (HCC), yet post-TACE tumor recurrence remains a critical challenge. Our single-cell RNA analysis reveals that tumor recurrence is mechanistically linked to TACE-induced expansion of PD-L1⁺ myeloid-derived suppressor cells (MDSCs).To counterbalance these paradoxical effects, we developed a self-degradable microsphere (MS) composed of hyaluronic acid and gelatin for sustained local delivery of the anti-PD-L1 antibody Envafolimab (KN035) to reshape the immunosuppressive tumor microenvironment (TME). Comprehensive characterization validated KN035-MS's spherical morphology, high drug-loading efficiency, and controlled release kinetics. In BALB/c-hPD-L1 murine HCC models, transhepatic arterial embolization with KN035-MS post-TACE achieved superior tumor suppression compared to systemic KN035 administration while demonstrating favorable biocompatibility. Mechanistically, KN035-MS effectively counteracted TACE-induced PD-L1⁺ MDSC infiltration and reprogrammed the TME by enhancing CD8+/CD4+ T-cell activation, increasing the number of innate lymphocytes (ILC), and polarizing macrophages toward an M1 phenotype. Critically, localized delivery via KN035-MS prolonged intratumoral drug retention, overcoming the rapid systemic clearance observed with conventional administration. These findings establish KN035-MS as a synergistic adjunct to TACE, addressing both inefficient drug delivery and postembolization immune evasion. This dual-mechanism strategy provides a clinically translatable approach to mitigate HCC recurrence, warranting further investigation in combinatorial locoregional-immunotherapy paradigms.

Mismatch repair‐deficient (dMMR) colorectal cancer (CRC) is characterized by poor response to traditional chemotherapy but heightened sensitivity to immune checkpoint inhibitors (ICIs). However, it is unclear whether envafolimab, a subcutaneous programmed death‐ligand 1 inhibitor, provides comparable efficacy and safety as a neoadjuvant treatment in these patients compared to programmed cell death‐1 inhibitors.

This open‐label, single‐arm phase 2 trial enrolled patients with locally advanced dMMR CRC. Participants received subcutaneous envafolimab (300 mg every 3 weeks) for three to four cycles. Tumor response was assessed using computed tomography/magnetic resonance imaging and endoscopy, with pathological response evaluated postsurgery. The primary end point was the complete response rate (CR), including clinical complete response (cCR) and pathological complete response (pCR). The secondary end points included R0 resection rate, 3‐year disease‐free survival, 5‐year overall survival, and treatment‐related adverse events (AEs).

Between August 22, 2022, to August 22, 2024, 15 patients were enrolled and received at least one dose of envafolimab. Two patients were excluded from efficacy analyses due to loss of follow‐up or patient refusal. Of the remaining 13 patients, seven (53.8%) achieved a complete response (two, cCR; five, pCR). The median time to CR was 3.1 months. Eleven patients underwent radical surgery, with no disease recurrence observed during follow‐up. Treatment‐related AEs were mild and of low incidence (28.6%), with only one patient experiencing a grade 3 fever. Subcutaneous administration of envafolimab demonstrated high patient convenience and satisfaction.

This preliminary study suggests that envafolimab is a promising effective and safe neoadjuvant option for locally advanced dMMR CRC; confirmation in larger cohorts is awaited.