There are some antibodies:

Recombinant mouse anti-CXCR4 antibody (12G5R)

Anti-CD184-dasatinib ADC

This antibody is a mouse monoclonal antibody that binds specifically to CXCR4, and it can neutralize the bioactivity of CXCR4.

This ADC product is composed of an anti-CD184 antibody conjugated via linker to dasatinib (anti-CXCR4-dasatinib). It has demonstrated a response in immunosuppressive drug treatment by a MOA (Mechanism of Action) of selectively delivering dasatinib to human T cells with excellent in vitro immunosuppressive activity.

What is CXCR4?

Chemokines are low molecular weight proinflammatory cytokines that can bind to G protein coupled receptors. It can attract and activate specific leukocytes in different immune inflammatory reactions. They play an important role in the tumorigenic transformation of cells and the process of tumor cells passing through the vascular endothelial and extracellular matrix. Chemokine 12 (CXCL12), also known as stromal cell derived factor 1, is a CXC chemokine. Chemokine receptor CXCR4 is a specific receptor for CXCL12. CXCL12 and its receptor CXCR4 play an important role in regulating the normal life process and the growth, proliferation, invasion and metastasis of tumor cells.

CXCR is a complete membrane protein, which specifically binds and modulates the cytokines of CXC chemokine family. They are a subfamily representing chemokine receptors. This is a large family of G-protein-linked receptors, known as seven transmembrane (7-TM) proteins—they cross the cell membrane seven times—CXCR4 is one of them, and has a high expression in human hematopoietic cells. CXCR4 gene, located on chromosome 4, is a G protein coupled receptor with seven transmembrane structures. The expression level of CXCR4 in colorectal cancer, breast cancer, ovarian cancer, melanoma, prostate cancer and other 20 kinds of human tumors was significantly higher than that in normal tissues. CXCR4 can promote tumor growth, metastasis, angiogenesis and drug resistance.

CXCR4 and proliferation, invasion and migration of tumor cells

Although specific expression of CC and CXCR has been found in many tumor cells, CXCR4 is the most common tumor cell CXCR in both human and experimental mice. Up to now, CXCR4 expression has been found in at least 23 different epithelial cells, mesenchymal tissues or hematopoietic tumor cells. However, CXCR4 is not expressed in all tumor cells. The expression of CXCR4 was negative in some cell lines from ovarian cancer, leukemia, thyroid undifferentiated cancer and brain malignant glioma. In primary tumors such as ovarian cancer and non-small cell lung cancer, only a part of the tumor cells expressed CXCR4 positive. Many studies have confirmed that CXCR4-CXCL12 is closely related to tumor cell migration and infiltration. CXCR4 can stimulate tumor cells to migrate in a directed manner and dip into basement membrane, endothelial cells, bone marrow or monolayer fiber cells along the gradient of CXCL12.

In some types of tumor tissue, CXCL12 can promote the proliferation of tumor cells and enhance the survival ability of tumor cells in adverse environment. CXCR4-CXCL12 can make tumor cells grow in unsuitable environment far away from primary focus. At present, the significance of the increased level of CXCL12 in the primary focus of tumor cells is not very clear. Although a certain level of CXCL12 can stimulate tumor growth and improve tumor cell viability, there is no clear evidence that this phenomenon is related to tumor metastasis.

In tumor cells, CXCR4 needs other factors to participate in the tumor growth process. CXCL12 can activate ovarian cancer cell line to produce tumor necrosis factor α, which, together with other cytokines, forms tumor cell factor network and promotes tumor growth. CXCR4 can induce the production of VEGF, an angiogenic factor, which has important biological functions such as increasing vascular permeability, promoting endothelial cell proliferation and promoting angiogenesis.

In addition to CXCR4, there are many CXCRs involved in the occurrence and development of tumors. Many tumor cells can express CXCR4, CC and CXC at the same time. Different types of CXCR are related to tumor metastasis. However, the mechanism of synergistic effect of multiple CXCRs in tumor cells is not clear, which needs further study.

CXCR4 and distant metastasis of tumor

The tumor model can help researchers further understand the role of CXCR4-CXCL12 in tumor distant metastasis. Biopsy of human ovarian cancer showed that CXCR4 was only expressed in a few primary tumors. However, if high expression of CXCR4 occurs in ovarian cancer cells with low CXCR4 receptor level, the migration and invasion ability of tumor cells guided by CXCL12 in vitro will be significantly enhanced; at the same time, the ability of tumor cells to adhere to extracellular matrix and the survival ability of tumor cells mediated by CXCL12 under adverse conditions will be significantly improved.

CXCR4 and the progress of tumor diagnosis and treatment

It was found that CXCR4 was expressed in many tumor cells, which was closely related to the growth, apoptosis, metastasis and invasion of tumor cells. Many animal experiments have confirmed that CXCR4 can be used as a new target of tumor therapy. An animal experiment on colon cancer found that after tumor cells were transfected with CXCL12, chemokines could bind to CXCR4 in the endoplasmic reticulum, thus preventing the expression of CXCR4. Blocking the combination of CXCL12 and CXCR4 can greatly reduce the probability of lung or liver metastasis of colon cancer. Anti CXCR4 antibody can inhibit the lymphatic metastasis of breast cancer. Using anti CXCR4 antibody or anti CXCL12 antibody to treat lymphoma stem cells can slow down the growth rate and reduce the tumor volume of lymphoma mice. CXCR4 antibody can also prevent the occurrence of tumor.

CXCR4 is widely found in a variety of cancer cells. Preliminary studies show that it is closely related to the growth, invasion and metastasis of tumor cells in vivo. Animal experiments and clinical studies have confirmed that CXCR4 receptor antagonists can inhibit the growth and spread of tumors. However, CXCR4 and its ligands are also widely present in the intracellular environment and inflammatory process. CXCR4 antagonists can activate hematopoietic stem cells in bone marrow. Therefore, the application of CXCR4 antagonists in cancer treatment may cause serious adverse reactions. Up to now, the relationship between CXCR4 signal transduction and oncogenes and the progression of malignant tumors is still poorly understood. Further study of CXCR4 is needed and will be helpful to explore more effective new tumor treatment methods.