A novel humanized anti-PD-1 monoclonal antibody potentiates therapy in oral squamous cell carcinoma

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Immune checkpoint inhibitors improve survival in many cancers.
• Limited research exists on immune checkpoint inhibition for oral squamous cell carcinoma (OSCC).
• Programmed cell death-1 (PD-1) and its ligand PD-L1 are key regulators of immune responses.

Purpose of the Study:

• To evaluate a novel anti-PD-1 monoclonal antibody (mAb) lacking C_H1 and C_L fragments for OSCC treatment.
• To investigate the therapeutic potential of this mAb in vitro and in vivo.
• To explore the underlying molecular mechanisms involving PD-L1, AKT, and ERK1/2 pathways.

Main Methods:

• Screening and isolation of a novel anti-PD-1 mAb.
• In vitro assays assessing T cell cytokine secretion, cellular lysis, and apoptosis.
• In vivo studies evaluating tumor growth inhibition and inflammation reduction in OSCC models.
• Analysis of PD-L1 expression and its correlation with AKT and ERK1/2 pathway activity.

Main Results:

• The novel anti-PD-1 mAb significantly enhanced T cell-mediated cytokine secretion.
• The mAb promoted cellular lytic and apoptotic activities, inhibited tumor growth, and reduced inflammation in vivo.
• PD-L1 blockade correlated with the inhibition of AKT and ERK1/2 signaling pathways.
• PD-L1 expression was detected in human OSCC tissues and adjacent normal oral mucosa.

Conclusions:

• The novel anti-PD-1 mAb demonstrates significant therapeutic potential for OSCC.
• The PD-L1/PD-1 signaling pathway modulates OSCC tumorigenesis via AKT and ERK1/2 pathways.
• This novel mAb represents a promising candidate for clinical therapy in human OSCC.