A humanized monoclonal antibody directed against the tumor-associated antigen (TAA) claudin-1 (CLDN1; CLDN-1), with potential immunostimulating and antineoplastic activities. Upon administration, eclutatug targets and binds to a specific extracellular loop epitope that is exposed in non-junctional (NJ) CLDN1 expressed on certain tumor cells. This prevents CLDN1-mediated signaling, which disrupts the stiff extracellular matrix (ECM) in tumors and, by disturbing the physical barrier, enhances the infiltration of immune cells, such as natural killer cells (NKs) and T-cells. This abrogates immunosuppression in the tumor microenvironment (TME) and leads to NK- and T-cell-mediated tumor cell killing. In addition, eclutatug can directly kill CLDN1-expressing tumor cells via antibody-dependent cell mediated cytotoxicity (ADCC). CLDN1, which is normally confined within the tight junctions in epithelial tissues, is overexpressed on a variety of tumor cells in a non-junctional form. CLDN1 overexpression on tumor cells correlates with ECM remodeling and T-cell exclusion, and is associated with reduced efficacy of checkpoint inhibitors (CPIs).