A Novel Vaccine Targeting Glypican-3 as a Treatment for Hepatocellular Carcinoma.
Mol Ther
; 25(10): 2299-2308, 2017 10 04.
Article
in En
| MEDLINE
| ID: mdl-28865999
ABSTRACT
Hepatocellular carcinoma (HCC) has a high morbidity and mortality rate worldwide, with limited treatment options. Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored glycoprotein that is overexpressed in most HCC tissues but not in normal tissues. GPC3-targeting antibody therapy shows limited response in a clinical trial due to the lack of a tumor-specific cytotoxic T lymphocyte (CTL) response. Here, in C57/B6 mice, we demonstrated that intravenous infusion of GPC3-coupled lymphocytes (LC/GPC3+) elicited robust GPC3-specific antibody and CTL responses, which effectively restricted proliferation and lysed cultured-HCC cells. Treatment with LC/GPC3+ induced durable tumor regression in HCC-bearing C57/B6 mice. Administration of LC/GPC3+ induced elevated levels of the cytotoxic T cell bioactive factors tumor necrosis factor alpha (TNF-α), interferon-γ (IFN-γ), granzyme B, and perforin, and substantially increased the number of infiltrating CD8+ T cells in tumor tissues. Moreover, immune responses elicited by LC/GPC3+ selectively suppressed GPC3+ tumors, but didn't affect the GPC3- tumors in BALB/c mice. Our findings provide the first preclinical evidence that intravenous infusion of the LC/GPC3+ complex can induce a strong anti-HCC effect through regulating systemic and local immune responses. These results indicate that the LC/GPC3+ complex could be developed as precision therapeutics for HCC patients in the future.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Cancer Vaccines
/
Glypicans
Limits:
Animals
Language:
En
Journal:
Mol Ther
Journal subject:
BIOLOGIA MOLECULAR
/
TERAPEUTICA
Year:
2017
Document type:
Article
Affiliation country:
United States