Syntheses and Immunological Evaluation of Self-Adjuvanting Clustered N-Acetyl and N-Propionyl Sialyl-Tn Combined with a T-helper Cell Epitope as Antitumor Vaccine Candidates

Tsung-Che Chang; Yoshiyuki Manabe; Yukari Fujimoto; Shino Ohshima; Yoshie Kametani; Kazuya Kabayama; Yuka Nimura; Chun-Cheng Lin; Koichi Fukase

doi:10.1002/anie.201804437

Syntheses and Immunological Evaluation of Self-Adjuvanting Clustered N-Acetyl and N-Propionyl Sialyl-Tn Combined with a T-helper Cell Epitope as Antitumor Vaccine Candidates

Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8219-8224. doi: 10.1002/anie.201804437. Epub 2018 Jun 7.

Authors

Tsung-Che Chang¹, Yoshiyuki Manabe^{1

2}, Yukari Fujimoto³, Shino Ohshima⁴, Yoshie Kametani⁴, Kazuya Kabayama^{1

2}, Yuka Nimura¹, Chun-Cheng Lin⁵, Koichi Fukase^{1

2}

Affiliations

¹ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
² Core for Medicine and Science Collaborative Research and Education, Project Research Center for Fundamental Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
³ Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
⁴ Faculty of Medicine, School of Medicine, Tokai University, 143 Shimokasuya, Isehara-shi, Kanagawa, 259-1193, Japan.
⁵ Department of Chemistry, National Tsing Hua University, 101 Sec. 2, Kuang Fu Rd., Hsinchu, 30013, Taiwan.

PMID: 29768704
DOI: 10.1002/anie.201804437

Abstract

Sialyl-Tn (STn) is a tumor-associated carbohydrate antigen (TACA) rarely observed on healthy tissues. We synthesized two fully synthetic N-acetyl and N-propionyl STn trimer (triSTn) vaccines possessing a T-helper epitope and a TLR2 agonist, since the clustered STn antigens are highly expressed on many cancer cells. Immunization of both vaccines in mice induced the anti-triSTn IgG antibodies, which recognized triSTn-expressing cell lines PANC-1 and HepG2. The N-propionyl triSTn vaccine induced the triSTn-specific IgGs, while IgGs induced by the N-acetyl triSTn vaccine were less specific. These results illustrated that N-propionyl triSTn is a valuable unnatural TACA for anticancer vaccines.

Keywords: adjuvants; antigens; cancer vaccines; carbohydrates; sialyl-Tn.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neoplasm / immunology
Antigens, Tumor-Associated, Carbohydrate / chemistry
Antigens, Tumor-Associated, Carbohydrate / immunology*
Cancer Vaccines / chemical synthesis
Cancer Vaccines / immunology*
Cattle
Cell Line, Tumor
Epitopes / chemistry
Epitopes / immunology*
Hep G2 Cells
Humans
Immunoglobulin G / immunology
Mice
Mice, Inbred BALB C
Serum Albumin, Bovine / chemistry
T-Lymphocytes, Helper-Inducer / cytology
T-Lymphocytes, Helper-Inducer / metabolism

Substances

Antibodies, Neoplasm
Antigens, Tumor-Associated, Carbohydrate
Cancer Vaccines
Epitopes
Immunoglobulin G
sialosyl-Tn antigen
Serum Albumin, Bovine