RecombiMAb anti-mouse CCR8

About RecombiMAb anti-mouse CCR8

The C8Mab-2-CP080 monoclonal antibody is a recombinant, chimeric version of the original C8Mab-2 antibody. The variable domain sequences are identical but the constant region sequences have been switched from Rat IgG2b, κ to Mouse IgG2a, κ for use in murine models. Species-matched chimeric antibodies exhibit regulated effector functions—including Fc receptor binding and complement activation—and result in less immunogenicity and formation of anti-drug antibodies (ADAs) than xenogenic antibodies in animal models. The anti-tumor activity of anti-CCR8 antibodies has been demonstrated to require Fc-mediated effector function with studies confirming the superior mouse IgG2a antibody binding to mouse FcγRIII and mouse FcγRIV is crucial for NK cell-mediated ADCC and macrophage-mediated ADCP in mice. The highly controlled sequence and lack of genetic drift in recombinant antibodies also provides more reliable and reproducible results over hybridoma derived antibodies. The C8Mab-2 monoclonal antibody recognizes the N-terminal region (1–33 amino acids) of mouse C-C chemokine receptor type 8 (CCR8), also known as CKR-8, CDw198, CMKBRL2, CMKBR8, and GPRCY6. CCR8 is a seven-pass transmembrane chemokine receptor and a member of the G protein-coupled receptor (GPCR) family. CCR8 ligands include CCL1, CCL16, and CCL8 (mCCL8) or CCL18 (hCCL18, a functional analog of mouse CCL8). Human and mouse CCR8 as well as its primary ligand CCL1 are structurally related, and this ligand is critical for skin homing of T cells and the survival of the regulatory T cells (Tregs) as well as their chemotaxis into tumors. CCR8 is predominantly expressed on activated Tregs marking the most suppressive and proliferative Treg population residing in the TME. Regulatory T cells (Tregs) are immunosuppressive cells essential for maintaining peripheral immune tolerance and preventing harmful autoimmune responses. A deficiency in their number or function can lead to the development of autoimmune disorders. Conversely, an abundance of Tregs, particularly a high Treg-to-CD8+ T effector cell ratio, can hinder anti-tumor immune surveillance and promote cancer progression. CCR8, a surface receptor selectively expressed on activated Tregs within tumors, has emerged as a promising therapeutic target. Its selective expression offers the potential to enhance anticancer responses while minimizing the safety risks associated with earlier systemic Treg-targeting strategies. Recent in-vivo studies have documented the involvement of CCR8 in type 2 inflammatory diseases, including atopic dermatitis (AD) and allergic enteritis (AE). In the tumor microenvironment, CCR8+ Treg numbers directly correlate with an advanced state of cancer, and therapeutic depletion of CCR8+ tumor-infiltrating Tregs (ti-Tregs) is shown to exert antitumor immunity and synergism with anti-PD-1 therapy.