Dual-recognizing antibodies targeting CEACAMs in the tumor microenvironment: towards more precise targeting

The tumor microenvironment (TME) is a dynamic and constantly evolving milieu surrounding cancer cells, comprising numerous components that influence tumor growth. The Carcinoembryonic Antigen-Related Cell Adhesion Molecule (CEACAM) family has been found to be abnormally expressed in various cancers, and recent studies have highlighted its critical role in shaping and regulating the TME. Several antibody drugs targeting the CEACAM family have been developed over the last years. However, due to the physiological expression of CEACAMs in normal tissues, most of these targeted agents have yielded unsatisfactory clinical trial outcomes, characterized by significant toxicity and limited efficacy. In view of this, enhancing therapeutic efficacy while reducing adverse effects has become a focal point of current research. This review systematically summarizes the structural features of the CEACAM family and the intrinsic mechanistic differences underlying their tumor-promoting effects, and discusses the limitations of existing clinical drugs. Based on antibody optimization strategies, we propose a conceptual framework of "dual-recognition" antibodies and elaborate on precision targeting approaches at three levels-epitope, molecular, and environmental-to provide directional guidance for future investigations.