Conventional and Chemically Programmed Asymmetric Bispecific Antibodies Targeting Folate Receptor 1

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Sep 10

PMID 31497024

Citations 3

Authors

Junpeng Qi

David Hymel

Christopher G Nelson

Terrence R Burke Jr

Christoph Rader

Affiliations

Soon will be listed here.

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 and 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.

Citing Articles

Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors.

Middelburg J, Kemper K, Engelberts P, Labrijn A, Schuurman J, van Hall T Cancers (Basel). 2021; 13(2).

PMID: 33466732 PMC: 7829968. DOI: 10.3390/cancers13020287.

Chemically Programmable and Switchable CAR-T Therapy.

Qi J, Tsuji K, Hymel D, Burke Jr T, Hudecek M, Rader C Angew Chem Int Ed Engl. 2020; 59(29):12178-12185.

PMID: 32329959 PMC: 7429910. DOI: 10.1002/anie.202005432.

Site-Specific Lysine Arylation as an Alternative Bioconjugation Strategy for Chemically Programmed Antibodies and Antibody-Drug Conjugates.

Hwang D, Tsuji K, Park H, Burke Jr T, Rader C Bioconjug Chem. 2019; 30(11):2889-2896.

PMID: 31675216 PMC: 7518637. DOI: 10.1021/acs.bioconjchem.9b00609.

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