CD70 Gene Editing    

CD70 (encoded by the Tumor Necrosis Factor ligand Superfamily member 7 (TNFSF7) gene) is a co-stimulatory factor present on B-cells, activated T-cells, and dendritic cells. In addition, CD40 stimulation in combination with innate cues such as type-I-Interferon and alpha-galacto-sylceramide induce robust CD70 expression on DC. Constitutive CD70 expression was found by medullary thymic epithelial cells (mTEC) and radio-resistant antigen presenting cells (APC) in the lamina propria of the intestine. The interaction with its ligand, CD27, is involved in proliferation, survival, and lymphocyte differentiation. CD70 is not expressed in non-lymphoid normal tissue but is overexpressed in tumor cells of various solid cancers. This high expression may induce cytotoxic effects in T-cells and B-cells, induce lymphocyte apoptosis, and promote escape from the immune system. Moreover, many in vitro studies have shown that CD70 overexpression by tumor cells can induce an anti-tumor response through T-cells in breast cancer cell lines.

CD70-CD27 in Tumor Biology

The TNF receptor superfamily member CD27 is a tightly regulated costimulatory molecule, activated by its unique ligand CD70, enabling activation of innate and adaptive immunity. In humans, CD27 expression is detected on thymocytes and naïve T cells, upregulated upon T cell activation and decreased after effector T cell differentiation. Moreover, CD27 is also found on central memory T cells, residing in secondary lymphoid organs. The role of the CD70/CD27 axis in T cell priming was also confirmed in various immunization and infection models. CD27-CD70 interactions can induce proliferation and cytokine production by both CD4+ and CD8+ T cells and promote development of cytotoxic T cell responses. When CD70 binds to CD27, the extracellular domain soluble CD27 (sCD27) of membrane-bound CD27, is cleaved from the cell surface by metalloproteinases. This 32 kDa protein has been detected in plasma, serum and urine samples from healthy individuals by enzyme-linked immunosorbent assay, and at increased levels in hematological malignancies and auto-immune diseases. In addition, sCD27 levels were particularly elevated in HIV+ patients who developed AIDS-associated non-Hodgkin lymphoma (NHL). The soluble form of CD27 has also been associated with poor outcome in various hematological malignancies, such as Waldenström's macroglobulinemia (WM), an indolent B cell malignancy characterized by bone marrow infiltration with lymphoplasmacytic cells (LPCs). Elevated serum concentrations of sCD27 were also found in patients with, chronic lymphocytic leukemia, acute lymphoblastic leukemia and large B cell lymphoma, which predicted poor outcome in the latter and correlated with CD27 expression on lymphoma cells.

Figure 1. CD70-CD27 pathway. (Jacobs J, et al., 2015)

CD70 as A Therapeutic Target in Tumor Therapy

The CD70-CD27 system is considered as a promising target for immunotherapy owing to its strong costimulatory activity. It has been reported that transgenic mice expressing CD70 constitutively in B-cells or dendritic cells have superior tumor control and that antibody blockade of CD27 inhibits the CD70-dependent anti-tumoral activity of CD40-activated dendritic cells. In addition, treatment with agonistic CD27-specific antibodies or CD27-stimulatory variants of soluble CD70 elicited tumor rejection in animal models. Therefore, CD70 encoding DNAs/RNAs, CD70-transfected dendritic cells and agonistic CD27-specific antibodies are currently under investigation in preclinical and clinical trials as adjuvants in immunotherapeutic concepts. First clinical trials with autologous monocyte-derived dendritic cells electroporated with mRNA mixtures encoding constitutively active Toll-like receptor 4 (TLR4), CD40L and CD70 along with human leukocyte antigen (HLA)-class II targeted fusion proteins of melanoma associated antigens (e.g., gp100, MAGE-A3, tyrosinase) showed good tolerance and provided initial evidence for objective responses in patients with stage III/IV melanoma.

CD70 Gene Editing Services

CRISPR/Cas9 Platform^CB, one of the leading biotechnological companies specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene-editing services to a wide range of genomics researchers. Based on our platform, we can help you effectively CD70 gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• CD70 Gene Knockout: We offer CD70 gene knockout cell line and knockout animal model generation service with high quality. Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements. Our one-stop KO animal model generation service covers from sgRNA design and construction, pronuclear microinjection to Founders genotyping and breeding.
• CD70 Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop CD70 knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of CD70 knock-in cell line generation projects, including stem cells, tumor cells and even difficult-to-handle cells. We also have extensive experience in incorporating CRISPR/Cas9 technology into animal models, which have been fully recognized by our clients.

If you have any questions, please feel free to contact us.

Related Products at CRISPR/Cas9 Platform^CB