Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice

Abstract

Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.

Materials for Immunotherapy

“…In 2012, Xu and co‐workers developed a similar liposomal system embedded with MHC II complexes to display antigenic OVA, which resulted in CD4 + T cell activation and anti‐OVA antibody production . Later, Nakatsura and co‐workers used liposomes displaying glypican‐3 (GPC3) antigens with CpG ODN adjuvants to induce GPC3‐specific CTLs and inhibit GPC3‐expressing hepatocellular carcinoma . The following year, Wyatt and co‐workers employed liposomes with envelope glycoproteins conjugated to their surfaces to activate B cells against HIV‐1 …”

Glypican‐3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment

“…Nakatsura and co-workers conducted a study to effectively enhance the antitumor reactivity of GPC3-derived epitope peptides in vivo, and reported that liposome-coupled GPC3 peptides induced peptide-specific CTLs at a lower dose than did a conventional vaccine emulsified in incomplete Freund's adjuvant. 146 Additionally, programmed death-1/programmed death ligand-1 blockade has been reported to augment the antitumor effects of the GPC3-derived peptide vaccine by increasing the immune response of vaccine-induced CTLs. 147 Through this work, Nakatsura and co-workers have provided a foundation for the clinical development of combination therapy involving the use of GPC3 peptide vaccines with other medications.…”

Advances in the study of oncofetal antigen glypican-3 expression in HBV-related hepatocellular carcinoma

“…However, molecular therapy remains a challenge mainly due to lack of specific targets. Use of the GPC-3 antigen as a target for HCC has been investigated with siRNA (47), vaccines (48,49), T lymphocytes (50)(51)(52), and anti-GPC-3 antibodies in vitro and in vivo (53,54). Some advances on the use of GPC-3 as the novel target for HCC therapy have been made (55).…”