CD27 drug cell screening model

CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily, also known as TNFRSF7. CD27 protein is mainly expressed in lymphocytes, including various types of T cells, B cells and NK cells. Existing studies have shown that it can interact with the CD70 protein expressed on different cells (including a variety of tumor cells). CD70 is mainly expressed in activated T cells, B cells and mature dendritic cells. CD27 activation can activate downstream NFkB and MAPK/JNK signaling pathways, TRAF2 and TRAF5 proteins also play an important role in CD27 signaling. By activating these pathways, the interaction of CD70 and CD27 can promote the activation, proliferation and differentiation of T cells and B cells. Therefore, CD27 plays an important role in immune regulation and is a key target for the treatment of cancer and inflammatory diseases.

CD27 protein has multiple biological functions

1. Activating macrophages to enhance phagocytic function;

2. Stimulate the activation and expansion of original CD4+ and CD8+ T cells, and promote the activation of CD8+ T cells;

3. After CD27 on the surface of T cells and NK cells is activated, it can increase the secretion of INF-γ and promote the activation and penetration of myeloid cells;

4. Promote the survival of B cells and DC-induced cytotoxic T cells;

5. Induce helper T cell 1 (Th1) to enhance differentiation and inhibit helper T cell 17 (Th17) differentiation;

6. In the T cell-dependent B cell response, CD27 promotes the expansion of activated B cells and the differentiation into plasma cells.

CD27 drug development status

At present, CD27 drugs are mainly agonist proteins, which promote cytotoxic T cell responses and kill tumor cells by activating CD27, recruiting effector cells and targeting immune regulatory receptors, and can be used in combination with other tumor immune drugs. There is no CD27 drug on the market yet. The fastest R&D progress is Celldex's Varlilumab and Aduro's MK-5890, both of which are in the second clinical phase. In addition, some preclinical CD27 inhibitory drugs have been studied to treat autoimmune diseases.

1. Celldex Varlilumab is an activating CD27 fully humanized monoclonal antibody targeting lymphocytes, which induces an anti-tumor response. Due to the limited expression and regulatory functions of CD27, targeting CD27 may cause less toxicity. Currently, Varlilumab is in a Phase II clinical study of colorectal cancer, metastatic melanoma, ovarian cancer, renal cell carcinoma, head and neck squamous cell carcinoma and glioblastoma.

2. Aduro MK-5890 is an anti-CD27 agonist jointly developed with Merck. It is currently undergoing a phase II clinical trial for the treatment of non-small cell lung cancer (NSCLC), evaluating pembrolizumab combined with MK-5890 for the treatment of anti-PD-L1 The effectiveness and safety of the treatment in patients with advanced squamous or non-squamous NSCLC.

In response to the needs of CD27 drug development and research, we have developed the CD27/NFκB-Luc/Jurkat drug screening cell line. Welcome to inquire.