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Conventional and Chemically Programmed Asymmetric Bispecific Antibodies Targeting Folate Receptor 1.
Qi, Junpeng; Hymel, David; Nelson, Christopher G; Burke, Terrence R; Rader, Christoph.
Afiliación
  • Qi J; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States.
  • Hymel D; Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United States.
  • Nelson CG; Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United States.
  • Burke TR; Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, United States.
  • Rader C; Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States.
Front Immunol ; 10: 1994, 2019.
Article en En | MEDLINE | ID: mdl-31497024
ABSTRACT
T-cell engaging bispecific antibodies (biAbs) can mediate potent and specific tumor cell eradication in liquid cancers. Substantial effort has been invested in expanding this concept to solid cancers. To explore their utility in the treatment of ovarian cancer, we built a set of asymmetric biAbs in IgG1-like format that bind CD3 on T cells with a conventional scFv arm and folate receptor 1 (FOLR1) on ovarian cancer cells with a conventional or a chemically programmed Fab arm. For avidity engineering, we also built an asymmetric biAb format with a tandem Fab arm. We show that both conventional and chemically programmed CD3 × FOLR1 biAbs exert specific in vitro and in vivo cytotoxicity toward FOLR1-expressing ovarian cancer cells by recruiting and activating T cells. While the conventional T-cell engaging biAb was curative in an aggressive mouse model of human ovarian cancer, the potency of the chemically programmed biAb was significantly boosted by avidity engineering. Both conventional and chemically programmed CD3 × FOLR1 biAbs warrant further investigation for ovarian cancer immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Anticuerpos Biespecíficos / Receptor 1 de Folato Límite: Animals / Female / Humans Idioma: En Revista: Front Immunol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Anticuerpos Biespecíficos / Receptor 1 de Folato Límite: Animals / Female / Humans Idioma: En Revista: Front Immunol Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos