Varlilumab: Unlocking CD27’s Potential in Cancer Research

Varlilumab (CDX-1127) is a human monoclonal antibody developed by Celldex Therapeutics, targeting CD27, a critical member of the TNF receptor superfamily. CD27 is predominantly expressed on T cells, B cells, and natural killer (NK) cells, playing a pivotal role in immune cell activation, survival, and proliferation. Its interaction with the ligand CD70 triggers downstream signaling that supports immune effector function, making it a promising target for cancer immunotherapy.

Varlilumab is designed to exploit CD27’s role in immune activation to enhance anti-tumor responses. This antibody provides dual benefits: stimulating T-cell activation and effector responses while mitigating immune-suppressive elements within the tumor microenvironment. In preclinical and clinical studies, Varlilumab has been shown to increase the proliferation of cytotoxic T cells and inhibit the activity of regulatory T cells (Tregs), which are often elevated in tumors and contribute to immune evasion.

A significant aspect of Varlilumab’s therapeutic application is its compatibility with other immune-modulating agents, particularly checkpoint inhibitors like nivolumab, an anti-PD-1 antibody. Combining Varlilumab with nivolumab leverages complementary mechanisms, where Varlilumab activates immune cells, and nivolumab prevents tumor-driven immune suppression. This synergistic approach enhances the overall anti-tumor response, offering promising results in clinical trials for multiple cancer types, including melanoma and renal cell carcinoma.

By targeting CD27, Varlilumab represents an innovative strategy to reshape the tumor microenvironment and potentiate immune-mediated destruction of cancer cells, exemplifying the growing emphasis on combination immunotherapies in oncology.

Varlilumab is an immunomodulatory monoclonal antibody that targets CD27, a co-stimulatory receptor expressed primarily on T-cells. CD27 plays a critical role in enhancing T-cell activation, proliferation, and cytokine production, essential components of a robust and sustained immune response. By binding to CD27, Varlilumab amplifies T-cell activation, enabling a more effective immune response against tumors. This effect is particularly advantageous in the context of combination therapies involving immune checkpoint inhibitors. Checkpoint inhibitors relieve the suppression of T-cell activity mediated by inhibitory pathways such as PD-1/PD-L1 and CTLA-4, while Varlilumab ensures sustained T-cell activation and proliferation, creating a synergistic mechanism that enhances the anti-tumor immune response.

Beyond its role in immune activation, Varlilumab exerts direct anti-tumor effects through antibody-dependent cellular cytotoxicity (ADCC). This mechanism involves the recruitment of immune effector cells, such as natural killer (NK) cells, to target and destroy CD27-expressing cancer cells. The engagement of Fc receptors on NK cells by the Fc region of Varlilumab facilitates this process, leading to the targeted lysis of tumor cells. By combining immune system activation with ADCC-mediated direct cytotoxicity, Varlilumab demonstrates a multifaceted therapeutic approach.

Additionally, preclinical studies suggest that Varlilumab may influence the tumor microenvironment by reducing regulatory T-cell (Treg) populations, which are often associated with immune suppression in tumors. This shift not only enhances effector T-cell function but also helps to reverse immune evasion strategies employed by cancer cells. The ability to modulate both systemic and localized immune responses positions Varlilumab as a promising agent in cancer immunotherapy, with potential applications across a range of tumor types when used as a monotherapy or in combination with other immune-activating agents.

Our biosimilar product, Varlilumab biosimilar, offers researchers a cost-effective and high-quality alternative to study CD27-targeted therapies. Designed for research use only, it provides a reliable tool for advancing discoveries in immuno-oncology.

A biosimilar is a biologic product designed to be highly similar to an original reference product, matching its structure, function, and activity. Biosimilars provide researchers with accessible options for preclinical and exploratory studies without the high costs associated with original biologics.