Produktbeschreibung
CPB505 is a 2+2 symmetric tetravalent bispecific checkpoint inhibitor antibody with the same structure as human therapeutic Cadonilimab but designed to target mouse programmed cell death protein-1 (PD-1, CD279) and mouse cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) for use in murine models. Like Cadonilimab, CPB505 has two PD-1-blocking and two CTLA-4-blocking arms to confer high avidity in context of high checkpoint density such as within the tumor microenvironment. CPB505 also has an engineered null Fc-region through the incorporation of LALA-PG Fc-silencing mutations to prevent binding to Fcgamma receptors and C1q, minimizing ADCC, ADCP, and complement activation against checkpoint-expressing lymphocytes. The synergistic effect of Fc-null engineering and tumor-biased engagement are intended to reduce systemic immune-related toxicities that are common with conventional PD-1 plus CTLA-4 combinations, while maintaining robust antitumor activity. Unlike Cadonilimab, CPB505 contains the murine IgG2a constant region to reduce immunogenicity and the formation of anti-drug antibodies (ADAs) in mouse models. This bispecific is designed to simultaneously bind mouse PD-1 and mouse CTLA-4 on T cells, particularly tumor-infiltrating lymphocytes, to engage both checkpoints on the same or neighboring T cells and provide coordinated dual checkpoint blockade within the tumor microenvironment. Blocking PD-1 prevents interaction with PD-L1/PD-L2 and reverses PD-1-mediated inhibitory signaling, restoring T-cell activation, proliferation, and effector function against tumor cells. Concurrent CTLA-4 blockade reduces competition with CD28 for CD80/CD86, enhancing costimulatory signaling and promoting expansion and priming of effector T cells, further amplifying antitumor responses.
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