Bispecific antibodies that engage pIgR enrich in mucosa in cynomolgus monkeys.

Abstract

Therapeutic antibodies have limited access to barrier‑protected compartments such as the brain, lung and gastric mucosa, and kidney lumen, constraining their effectiveness in many diseases. Approaches using a bispecific antibody that targets a transcytosing receptor such as the polymeric Ig receptor (pIgR) can result in significant enrichment of IgG-based therapeutics across from blood into mucosal or mucosal lining. The polymeric Ig receptor is expressed in epithelial layers in many tissues, but differences in expression patterns across species represent a challenge in validating preclinical in vivo models. Here, we compare RNA and protein expression across an array of human, cynomolgus monkey, and mouse tissues. We show that pIgR expression in cynomolgus monkeys is similar to expression in humans. We further evaluate the ability of pIgR-targeted bispecific antibodies to transcytose into lung and gastrointestinal mucosa in cynomolgus monkeys. We show that pIgR-targeted bispecific antibodies rapidly deplete from serum, while enriching 5-10-fold in bronchoalveolar lavage fluid compared to normal IgG antibodies. These results support the use of anti-pIgR bispecific antibodies to treat diseases requiring targeting in mucosal areas.