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A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens.


ABSTRACT: Bispecific antibodies based on full-length antibody structures are more optimal than fragment-based formats because they benefit from the favorable properties of the Fc region. However, the homodimeric nature of Fc effectively imposes bivalent binding on all current full-length bispecific antibodies, an attribute that can result in nonspecific activation of cross-linked receptors. We engineered a novel bispecific format, referred to as mAb-Fv, that utilizes a heterodimeric Fc region to enable monovalent co-engagement of a second target antigen in a full-length context. mAb-Fv constructs co-targeting CD16 and CD3 were expressed and purified as heterodimeric species, bound selectively to their co-target antigens, and mediated potent cytotoxic activity by NK cells and T cells, respectively. The capacity to co-engage distinct target antigens simultaneously with different valencies is an improved feature for bispecific antibodies with promising therapeutic implications.

SUBMITTER: Moore GL 

PROVIDER: S-EPMC3242841 | biostudies-literature | 2011 Nov-Dec

REPOSITORIES: biostudies-literature

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A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens.

Moore Gregory L GL   Bautista Cristina C   Pong Erik E   Nguyen Duc-Hanh T DH   Jacinto Jonathan J   Eivazi Araz A   Muchhal Umesh S US   Karki Sher S   Chu Seung Y SY   Lazar Greg A GA  

mAbs 20111101 6


Bispecific antibodies based on full-length antibody structures are more optimal than fragment-based formats because they benefit from the favorable properties of the Fc region. However, the homodimeric nature of Fc effectively imposes bivalent binding on all current full-length bispecific antibodies, an attribute that can result in nonspecific activation of cross-linked receptors. We engineered a novel bispecific format, referred to as mAb-Fv, that utilizes a heterodimeric Fc region to enable mo  ...[more]

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