An antibody Fc engineered for conditional antibody-dependent cellular cytotoxicity at the low tumor microenvironment pH.

ABSTRACT: Despite the exquisite specificity and high affinity of antibody-based cancer therapies, treatment side effects can occur since the tumor-associated antigens targeted are also present on healthy cells. However, the low pH of the tumor microenvironment provides an opportunity to develop conditionally active antibodies with enhanced tumor specificity. Here, we engineered the human IgG1 Fc domain to enhance pH-selective binding to the receptor FcγRIIIa and subsequent antibody-dependent cellular cytotoxicity (ADCC). We displayed the Fc domain on the surface of mammalian cells and generated a site-directed library by altering Fc residues at the Fc-FcγRIIIa interface to support interactions with positively charged histidine residues. We then used a competitive staining and flow cytometric selecti

SUBMITTER: Liu Y 

PROVIDER: S-EPMC9006656 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature