Bi-specific Antibody Engagers for Cancer Immunotherapy

Overview

Journal Res Sq

Date 2024 Aug 16

PMID 39149504

Authors

Hidde Ploegh

Xin Liu

Camille Le Gall

Ryan Alexander

Ella Borgman

Thomas Balligand

Affiliations

Soon will be listed here.

Abstract

Bispecific antibody engagers are fusion proteins composed of a nanobody that recognizes immunoglobulin kappa light chains ( ) and a nanobody that recognizes either CTLA-4 or PD-L1. These fusions show strong antitumor activity in mice through recruitment of polyclonal immunoglobulins independently of specificity or isotype. In the MC38 mouse model of colorectal carcinoma, the anti-CTLA-4 conjugate eradicates tumors and reduces the number of intratumoral regulatory T cells. The anti-PD-L1 conjugate is less effective in the MC38 model, whilst still outperforming an antibody of similar specificity. The potency of the anti-PD-L1 conjugate was strongly enhanced by installation of the cytotoxic drug maytansine or a STING agonist. The ability of such fusions to engage the Fc-mediated functions of all immunoglobulin isotypes is an appealing strategy to further improve on the efficacy of immune checkpoint blockade, commonly delivered as a monoclonal immunoglobulin of a single defined isotype.

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