A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma

• Published in: Scientific reports Vol. 10; no. 1; p. 4021
• Main Authors: Tamai, Toshikatsu, Mizukoshi, Eishiro, Kumagai, Masashi, Terashima, Takeshi, Iida, Noriho, Kitahara, Masaaki, Shimakami, Tetsuro, Kitamura, Kazuya, Arai, Kuniaki, Yamashita, Taro, Sakai, Yoshio, Yamashita, Tatsuya, Honda, Masao, Fushimi, Kazumi, Kaneko, Shuichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-03-2020; Nature Publishing Group
• Subjects: 631/250; 631/67; Adult; Aged; Aged, 80 and over; alpha-Fetoproteins - immunology; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Cell proliferation; Drb1 protein; Enzyme-linked immunosorbent assay; Epitopes; Epitopes, T-Lymphocyte - immunology; Female; Hepatocellular carcinoma; Histocompatibility antigen HLA; Humanities and Social Sciences; Humans; Immunity, Cellular; Immunogenicity; Immunotherapy; Leukocytes (mononuclear); Liver cancer; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Lymphocytes T; Major histocompatibility complex; Male; Middle Aged; multidisciplinary; Neoplasm Proteins - immunology; Peptides; Peptides - immunology; Peripheral blood mononuclear cells; Science; Science (multidisciplinary); T-Lymphocytes - immunology; T-Lymphocytes - pathology; α-Fetoprotein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-60843-4

α-Fetoprotein (AFP) is considered a good target for immunotherapy strategies against hepatocellular carcinoma (HCC); however, no immunodominant AFP-derived MHC class II-restricted helper T-lymphocyte (HTL) epitope has been reported. Therefore, we identified novel AFP-derived HTL epitopes possessing high immunogenicity. HTL epitopes were predicted using the online service, and peptides were subsequently synthesized. Four newly synthesized peptides showed positive reactivity in >20% patients on ELISPOT using peripheral blood mononuclear cells (PBMCs). Among these, the highest rate was shown by AFP
1
(MKWVESIFLIFLLNFTESRT), which also showed the highest positive rate in cell proliferation assays. Binding assays demonstrated that AFP
1
had strong binding properties toward MHC molecules. Further, blocking assays performed using an anti-HLA-DR antibody showed that immune response decreased, confirming the binding of AFP
1
to HLA-DR molecules. Furthermore, the survival rates of patients with stages II–IV HCC indicated that T cell response against AFP
1
led to significantly greater survival that of patients without T cell response. When evaluating immune response against AFP
1
before and after HCC treatment, an increase in the frequency of peptide-specific T cells was observed after treatment in patients with HLA-DRB1*1502, *0405, and *0901 alleles. In conclusion, the identified epitopes may be useful for immunotherapy strategies against HCC.