Back to Search Start Over

Nucleic acid–triggered tumoral immunity propagates <scp>pH</scp> ‐selective therapeutic antibodies through tumor‐driven epitope spreading

Authors :
Genta Furuya
Hiroto Katoh
Shinichiro Atsumi
Itaru Hashimoto
Daisuke Komura
Ryo Hatanaka
Shogo Senga
Shuto Hayashi
Shoji Akita
Hirofumi Matsumura
Akihiro Miura
Hideaki Mita
Makoto Nakakido
Satoru Nagatoishi
Akira Sugiyama
Ryohei Suzuki
Hiroki Konishi
Asami Yamamoto
Hiroyuki Abe
Nobuyoshi Hiraoka
Kazunori Aoki
Yasumasa Kato
Yasuyuki Seto
Chihoko Yoshimura
Kazutaka Miyadera
Kouhei Tsumoto
Tetsuo Ushiku
Shumpei Ishikawa
Source :
Cancer Science. 114:321-338
Publication Year :
2022
Publisher :
Wiley, 2022.

Abstract

Important roles of humoral tumor immunity are often pointed out; however, precise profiles of dominant antigens and developmental mechanisms remain elusive. We systematically investigated the humoral antigens of dominant intratumor immunoglobulin clones found in human cancers. We found that approximately half of the corresponding antigens were restricted to strongly and densely negatively charged polymers, resulting in simultaneous reactivities of the antibodies to both densely sulfated glycosaminoglycans (dsGAGs) and nucleic acids (NAs). These anti-dsGAG/NA antibodies matured and expanded via intratumoral immunological driving force of innate immunity via NAs. These human cancer-derived antibodies exhibited acidic pH-selective affinity across both antigens and showed specific reactivity to diverse spectrums of human tumor cells. The antibody-drug conjugate exerted therapeutic effects against multiple cancers in vivo by targeting cell surface dsGAG antigens. This study reveals that intratumoral immunological reactions propagate tumor-oriented immunoglobulin clones and demonstrates a new therapeutic modality for the universal treatment of human malignancies.

Details

ISSN :
13497006 and 13479032
Volume :
114
Database :
OpenAIRE
Journal :
Cancer Science
Accession number :
edsair.doi.dedup.....b051d257c2a43ed9e392f271460958d8
Full Text :
https://doi.org/10.1111/cas.15596