| Background | Varlilumab (CDX-1127), a human IgG1κ monoclonal antibody, targets CD27 receptor through reacting with the ligand binding site of CD27. CD27 is a member of the tumor necrosis factor receptor superfamily and expressed on unstimulated T lymphocytes, serving as a potent costimulatory molecule. It has been found that CD27 induces a series of T-cell reactions including T-cell activation, proliferation, survival, and maturation of effector capacity and T-cell memory together with its ligand CD70, which is transiently expressed on antigen-presenting cells. Besides, the interaction of CD27 and CD70 also stimulate B-cell proliferation, generation of plasma cells, production of immunoglobulin and B-cell memory, and induction of the cytolytic activity of natural killer (NK) cells. Moreover, CD27 is considered to function on tumor expansion and activation as it also expressed by regulatory T cells (Tregs), a cell that is associated with the suppression of antitumor immunity. The drug, developed by Celldex Therapeutics, is designed for immunotherapy for patients with solid tumors and hematologic malignancies. Varlilumab is currently conducted with two trails. One is the phase 1B clinical trial for advanced breast or ovarian cancer in combination with ONT-10. Another is the phase 1/2 trial for advanced refractory solid tumors together with anti-PD-1 nivolumab. |
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