RecombiMAb anti-mouse PD-L1 (B7-H1)

Cancer cells adopt multiple strategies to avoid detection and destruction by the immune system, including exploiting immune checkpoint pathways. B7x (B7-H4, B7S1, or VTCN1), a member of the B7/CD28 family, is frequently expressed in advanced bladder cancer, yet its role in bladder cancer progression and resistance to therapy remains poorly understood. Resistance to PD-1/PD-L1 immune checkpoint blockade immunotherapy significantly limits durable responses, with only 20%-25% of patients with muscle-invasive bladder cancer (MIBC) achieving long-term benefits. Here, we demonstrated that B7x mRNA and protein expression were associated with poor survival outcomes in MIBC patients and mouse models of bladder cancer, respectively. Stable expression of B7x in immune-competent bladder cancer mouse models resulted in enhanced tumor growth and splenomegaly, driven by the exclusion and suppression of tumor-infiltrating antitumor immune cells and the enrichment of pro-tumor and immunosuppressive cells. Consistently, in the IMvigor210 clinical trial, high B7x mRNA expression was correlated with poorer survival in MIBC patients treated with PD-L1 blockade. Notably, combination therapy targeting B7x alongside PD-1/PD-L1 or CTLA-4 blockade reduced tumor burden and overcame resistance to monotherapy. These findings establish B7x as a substantial driver of immune evasion in bladder cancer and highlight its potential as a therapeutic target to improve immune checkpoint blockade efficacy in MIBC.

Peptides are an emerging class of biologics for cancer immunotherapy; however, their clinical translation is hindered by poor binding kinetics, bioavailability, and short plasma half-life compared to their corresponding antibodies. Nanoparticles present potential solutions but face scale-up difficulties due to complexity. Here, a translatable, modular nanoparticle scaffold is presented for peptide-based immune checkpoint inhibitors (ICIs). This platform is based on a simple structure of generation 7 (G7) poly(amidoamine) (PAMAM) dendrimers conjugated with engineered peptides (dendrimer-peptide conjugates, DPCs). DPCs functionalized with multiple copies of a programmed death-ligand 1 (PD-L1)-binding peptide exhibited significantly enhanced avidity-based binding kinetics and in vitro specificity, in addition to the substantially prolonged plasma half-life in vivo. Notably, a series of in vivo experiments revealed that DPCs displayed selective tumor accumulation and high efficacy, without apparent toxicity, when applied to a syngeneic mouse model bearing mouse oral carcinoma (MOC1) tumors. The results indicate that the DPC platform significantly improves the antagonistic effect and in vivo behaviors of the PD-L1-binding peptides, which can be potentially applied to virtually any peptide-based ICIs. The DPC platform's simplicity and modular nature will likely increase the potential of its clinical translation and ultimately enable precision/personalized cancer immunotherapy.

Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear.