Скачать или смотреть Varlilumab Unlocking CD27’s Potential in Cancer Research

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1. Introduction to Varlilumab:

Definition: Varlilumab (CDX-1127) is a human monoclonal antibody developed by Celldex Therapeutics that targets CD27.
Target: CD27 is a key member of the TNF receptor superfamily, predominantly expressed on T cells, B cells, and NK cells. It plays a crucial role in immune cell activation, survival, and proliferation.
Mechanism of Action (Overview): Varlilumab enhances immune responses by activating CD27 signaling, promoting T-cell proliferation, and regulating immune suppression in cancer.

2. Detailed Mechanism of Action:

T-cell Activation and Proliferation: "By binding to CD27, Varlilumab amplifies T-cell activation, enabling a more effective immune response against tumors." This includes enhancing cytokine production.
Synergy with Checkpoint Inhibitors: Varlilumab creates a synergistic mechanism with checkpoint inhibitors by ensuring sustained T-cell activation and proliferation. Checkpoint inhibitors relieve the suppression of T-cell activity.
Antibody-Dependent Cellular Cytotoxicity (ADCC): "Varlilumab exerts direct anti-tumor effects through antibody-dependent cellular cytotoxicity (ADCC)." This involves recruiting immune effector cells, particularly NK cells, to target and destroy CD27-expressing cancer cells. The Fc region of Varlilumab engages Fc receptors on NK cells, leading to tumor cell lysis.
Tumor Microenvironment Modulation: Preclinical studies suggest Varlilumab reduces regulatory T-cell (Treg) populations within the tumor microenvironment, which are associated with immune suppression. This shift enhances effector T-cell function and reverses immune evasion.

3. Clinical Applications and Trials:

Combination Therapy: Varlilumab has demonstrated potential in combination with other immunotherapeutic agents, most notably nivolumab (a PD-1 inhibitor).
Cancers Studied: The combination of Varlilumab and nivolumab has been studied in advanced cancers, including:
Melanoma
Glioblastoma
Hodgkin lymphoma
Glioblastoma: "Preliminary studies suggest that varlilumab may reinvigorate T-cell activity, making it a valuable adjunct to checkpoint inhibitors like nivolumab in this context." Glioblastoma is often resistant to treatment due to its immunosuppressive environment.
Refractory/Relapsed Cases: Varlilumab has shown promise in melanoma and Hodgkin lymphoma cases that have not responded to traditional therapies by activating CD27.
Discontinued Trials: "Although some clinical trials involving varlilumab have been discontinued, the insights derived from these studies remain critical" to informing future strategies.

4. Varlilumab Biosimilar:

Purpose: A cost-effective and high-quality alternative for researchers to study CD27-targeted therapies in preclinical studies.
Definition: "A biosimilar is a biologic product designed to be highly similar to an original reference product, matching its structure, function, and activity."
Benefits: Cost-effective, reliable (consistent quality), and accessible for global researchers.
Disclaimer: "The Varlilumab biosimilar is intended exclusively for research purposes and is not approved for clinical or therapeutic use."