Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma

Area of Science:

• Oncology
• Immunotherapy
• Biotechnology

Background:

• Hepatocellular carcinoma (HCC) is a challenging cancer with limited treatment options and poor patient outcomes.
• Aspartate β-hydroxylase (ASPH) is a cell surface enzyme frequently overexpressed in HCC, making it a potential therapeutic target.

Purpose of the Study:

• To evaluate the efficacy of nanoparticle lambda (λ) phage vaccine constructs targeting ASPH in murine models of HCC.
• To assess the immune responses generated by the ASPH-targeted vaccine.

Main Methods:

• Mice were immunized with nanoparticle λ phage vaccine constructs targeting ASPH before and after tumor implantation.
• Antitumor activity was assessed by measuring antigen-specific cellular immune responses and identifying tumor-infiltrating lymphocytes.
• Cytotoxicity and cytokine secretion (Th1 and Th2) were analyzed.

Main Results:

• Vaccination significantly inhibited HCC growth and progression in prophylactic and therapeutic settings.
• ASPH-specific CD4+ and CD8+ T lymphocytes were detected, exhibiting cytotoxicity against ASPH-expressing HCC cells.
• λ phage vaccination led to tumor necrosis and infiltration of CD3+ and CD8+ T cells, with efficacy confirmed in a metastatic model.

Conclusions:

• ASPH is a highly antigenic target suitable for HCC immunotherapy.
• Nanoparticle λ phage vaccines targeting ASPH demonstrate promising therapeutic potential for hepatocellular carcinoma.