Development of therapeutic PD-1 monoclonal antibodies for treatment of canine tumor.

Discovery and functional characterization of novel programmed death-ligand 1 monoclonal antibodies.

Background/aim Targeted therapies with monoclonal antibodies provide cancer patients with better prognosis and disease-free survival. The blockade of immune checkpoints, including programmed cell death protein-1 (PD-1) and its ligand PD-L1, with monoclonal antibodies may boost immune responses against tumors and is regarded as an effective strategy in cancer immunotherapy. We describe the generation of anti-PD-L1 monoclonal antibodies with high affinity and specificity, and we assess their potential for therapeutic use in cancer. Materials and methods Hybridomas were selected for PD-L1 specificity and cross-reactivity with other immune checkpoint proteins and PD-L1 orthologs using indirect ELISA. Immunofluorescence and Western blotting assays were conducted for further characterization of the antibodies. The affinities of the antibodies for PD-L1 were determined using surface plasmon resonance. Receptor blocking activities were examined through competitive ELISA and cell-based luciferase reporter assays. Sequences of variable regions of the selected antibodies were determined by Sanger sequencing and subjected to BLAST analysis. Results A total of 25 PD-L1-specific monoclonal antibodies were generated. While most clones reacted with PD-L1 from cynomolgus monkeys, none of the antibodies displayed cross-reactivity with other checkpoint proteins. Immunofluorescence assays showed that the selected clones stained PD-L1-expressing cell membranes specifically, but not those of PD-L1-negative cells. Western blotting revealed that most of the clones recognized both glycosylated and nonglycosylated PD-L1, and a few reacted with the glycosylated form only. Only two clones with subnanomolar affinity for human PD-L1 were effective at blocking PD-1/PD-L1 and CD80/PD-L1 interactions. Sequence analysis of their variable regions revealed their unique specificity. Conclusion Of the 25 monoclonal antibodies produced in this study, only one was identified as a potential therapeutic drug candidate thanks to its high capacity for checkpoint blockade and affinity, as well as its unique sequence specificity. These properties are comparable to those of anti-PD-L1 antibodies currently used in clinical practice.

Dual-targeting CD73/PD-L1 bifunctional inhibitor: a promising cancer immunotherapy strategy

CP-1 exhibits balanced, dual-nanomolar inhibitory activity against PD-L1 and CD73 and displays potent immunomodulatory effects at the cellular level and serves as a promising lead candidate for developing novel bifunctional agents to advance tumor immunotherapy.

Efficacy of Bioengineered PD-L1 siRNA for Immunotherapy Against Non-Small Cell Lung Cancer Cells

The potential of bioengineered PD-L1 siRNA entities for NSCLC immunotherapy is demonstrated and their immunotherapeutic efficacy against non-small cell lung cancer (NSCLC) in vitro is defined.

Envafolimab – novel anti-PD-1/PD-L1 antibody in cancer treatment

The landscape of immunotherapy in oncology has markedly advanced with the development of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) inhibitors, fundamentally reshaping cancer treatment by potentiating anti-tumor immune responses. PD-1/PD-L1 blockade agents, such as FDA-approved nivolumab, pembrolizumab, and dostarlimab, have demonstrated significant clinical efficacy across various malignancies. Additionally, investigational agents like envafolimab, a novel PD-L1 inhibitor, are currently under clinical evaluation for efficacy and safety in solid tumors. This review examines the emerging data on envafolimab and discusses strategies to optimize its therapeutic impact, including combination regimens and personalized approaches. Tailoring treatments based on individual genetic, immunological, and microbiome profiles holds the potential to enhance response rates and the durability of outcomes. The integration of these factors is pivotal in advancing the precision and success of immunotherapy in oncology.

Anti-PD-1 single-chain variable fragments in cancer immunotherapy: from molecular engineering to clinical translation

Safety, feasibility, and efficacy of anti-PD-1 therapy for the treatment of classical Hodgkin lymphoma.

The clinical paradigm for treatment of classical Hodgkin lymphoma has been transformed by the use of anti-PD-1 therapy, driven by foundational work revealing near-universal 9p24.1 alterations resulting in overexpression of PD-L1 and PD-L2 on Reed-Sternberg cells. Use of PD-1 inhibitors has demonstrated remarkable clinical activity for patients with Hodgkin lymphoma. Anti-PD-1 monotherapy has demonstrated durable remissions in the relapsed/refractory setting, including a 5-year overall survival of around 70% in clinical trials. Further efforts have evaluated these treatments in various combinations and demonstrated efficacy in both the salvage setting prior to stem cell transplantation (SCT) and the relapsed/refractory setting after SCT. After such promising results, these agents were moved into the frontline setting with landmark trials such as SWOG S1826, establishing Nivo-AVD (nivolumab, doxorubicin, vinblastine, dacarbazine) as an emerging standard for advanced-stage classical Hodgkin lymphoma. Similarly, Nivo-AVD in the NIVAHL trial demonstrated remarkable efficacy in early stage, unfavorable disease. These agents have a unique mechanism of action that shows promise for patients who would otherwise be chemotherapy-ineligible. The use of these agents is also of interest in the adolescent and young adult populations who would be at risk from long-term side effects of chemotherapy or radiation. This review seeks to examine the safety, efficacy, and feasibility of anti-PD-1 therapy in classical Hodgkin lymphoma.