Development of cancer vaccine using adjuvant function encrypted artificial antigens

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430172
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Masaki Ito 東京慈恵会医科大学, 医学部, 講師 (80297366)
• Co-Investigator(Renkei-kenkyūsha): SHIBA KIYOTAKA がん研究所, 蛋白創製研究部, 部長 (40196415)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: TLR4 / 抗原提示細胞 / 細胞性免疫 / Molcraft / OVA(Ovalbumin) / 人工抗原 / 人工タンパク質

Outline of Final Research Achievements

From a functional viewpoint, adjuvants are classified into two categories: “physical adjuvants” increase the efficacy of antigen presentation by antigen-presenting cells (APC) and “signal adjuvants” induce the maturation of APC. We created the artificial antigens by appending the TLR4 agonistic peptide motifs to create “adjuvant-free” vaccine. The antigens with TLR4 agonistic motifs have activated NF-κB signaling pathways through TLR4. These proteins also induced the maturation of APC in vitro. Unexpectedly, signal adjuvant-encrypted proteins have lost their ability to be physical adjuvants because they did not induce cytotoxic T lymphocytes in vivo. These results confirmed that the manifestation of a motif’s function is context-dependent and simple addition does not always work for motif-programing. Further optimization of the molecular context of the TLR4 agonistic motifs in antigens should be required to create adjuvant-free antigens.

Free Research Field

分子生物学