Development of Next-Generation Immunotherapy using Antitumor Antibodies armed with Bridging-BiTE against Refractory Tumors

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Ehime University
• Principal Investigator: Ochi Toshiki 愛媛大学, 医学系研究科, 講師 (10571086)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: がん免疫療法 / 二重特異性抗体

Outline of Final Research Achievements

In this study, we have developed a new modality, named as B-BiTE (Bridging-Bispecific T-cell Engager) by using gene-engineering technology. B-BiTE possesses two single chain fragment variables (scFvs) which are specific for human IgG-Fc and human CD3, respectively. B-BiTE can bind to an antitumor antibody, thereby generating a new bispecific antibody. A mAb/B-BiTE complex can activate human T cells while preserving human NK-cell reactivity which is mediated by a mAb itself. Therefore, a mAb/B-BiTE complex can induce enhanced in vivo antitumor effects as compared to those mediated by a mAb alone. B-BiTE can allow us to develop a panel of new bispecific antibodies from a series of clinically available mAbs, resulting in further advancement of next-generation antibody-based cancer immunotherapy.

Free Research Field

血液学・腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫療法は、難治性がんに対する新たな治療法として注目されているが、高額な費用が必要となることなど、多くのがん患者に還元するにはまだ多くの問題を抱えている。我々が確立した新規技術 -B-BiTE- を用いれば、これまでに開発された、またこれから開発される抗体医薬品にあらかじめB-BiTEを結合させるだけで、新たな二重特異性抗体を迅速かつ容易に作製することが可能となる。本技術によって、コストを抑えつつ、がん免疫療法の治療効果を幅広く増強することが期待できるため、免疫療法医薬品開発領域におけるインパクトは大きく、社会的意義も高いと考えられる。