Analyses of tumor cell-specific glycan structures for the development of next-generation immunotherapy for pancreatic cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17001
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Showa University
• Principal Investigator: Ohkuma Ryotaro 昭和大学, 医学部, 講師 (30833769)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: PIGR / Lectinアレイ / CAR-T

Outline of Final Research Achievements

Pancreatic cancer has a poor prognosis and warrants novel predictors of therapeutic efficacy and prognosis. We has demonstrated that Polymeric Immunoglobulin Receptor (PIGR) was involved in resistance against chemotherapies and poor prognosis of pancreatic cancer patients. Therefore, PIGR molecule has been identified as a candidate target antigen for novel CAR-T therapy. We are trying to create specific antibodies against PIGR to be loaded onto CAR-T cells. As soon as the antibodies against PIGR are obtained, we will construct CAR-T cells that bind specifically to PIGR, and load the currently identified “lectin-A” onto the CAR-T cells.
We intended to construct the CAR system that turns “ON” only when both lectin and antibody signals are received. We have already performed the consideration of conditions. The cytotoxic activity and cytokine production capacity of “Lectin-CAR” will be analyzed, and its anti-tumor effect and adverse events will also be investigated in further study.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

CAR-T療法の標的抗原の候補として、抗癌剤耐性に関わる分子や予後不良に関わる分子であるPIGRを同定した。しかしPIGRは一部正常細胞にも発現し、CAR-T療法の標的抗原として正常細胞をも傷害する問題がある。我々はPIGRにおける糖鎖発現を解析し、レクチンAが正常細胞と腫瘍細胞との識別に有用である可能性を示した。特定抗原における糖鎖修飾の違いに着目して、腫瘍細胞上の標的抗原の糖鎖修飾のみを認識するレクチンをCAR-T細胞に搭載するという発想は報告が乏しく、学術的意義は高い。また安全性の高いCAR-T療法の開発に応用できる可能性があり、治療法が少ない膵臓がん患者に対する意義は大きいと考える。