Ulocuplumab Overview

Introduction of Ulocuplumab

Ulocuplumab is a fully human IgG4 monoclonal antibody targeted CXC chemokine receptor 4 (CXCR4), which is highly expressed in different hematological malignancies including chronic lymphocytic leukemia (CLL). This drug was developed by Bristol-Myers Squibb in an attempt for the treatment of hematologic malignancies. In 2014, ulocuplumab was studied in a phase Ib study of relapsed or refractory multiple myeloma combined with lenalidomide plus low-dose dexamethasone or bortezomib plus dexamethasone. The safety, tolerance, pharmacokinetics, pharmacodynamics and clinical activity of the combination were tested. The results showed that the blocking of CXCR4-CXCL12 axis by ulocuplumab was safe and the antibody had the prospect of becoming a new anti-myeloma drug. In 2016, ulocuplumab was used in the treatment of CLL, with plerixafor-mozobil, a small molecular inhibitor of CXCR4, as the control. The results supported the biological activity of ulocuplumab in CLL and provided a basis for follow-up clinical research.

Mechanism of Action of Ulocuplumab

Ulocuplumab is a monoclonal antibody which can bind to CXCR4 specifically and has potential anti-tumor activity. CXCR4, also known as fusin, is a specific α-chemokine receptor of stromal cell derived factor-1 (SDF-1), and SDF-1 is the only ligand of CXCR4. Because of this one-to-one binding relationship and high affinity, they constitute the SDF-1/CXCR4 biological axis, which is closely related to cell-to-cell information transmission and cell migration, and participates in many physiological processes. These include regulation of embryonic development, homing of stem cells, and lymphocyte chemotaxis. In addition, CXCR4 expression in various tumors, such as lung cancer, leukemia, breast cancer, prostate cancer, ovarian cancer and so on. Studies have found that CXCR4 has a direct or indirect role in the promotion of tumor progression. The tumor cells expressing CXCR4 migrated under the action of CXCR4/CXCL12 axis and homed to the site of non-malignant interstitial cells expressing CXCL12. These results suggest that the metastasis of tumor cells is regulated by chemokine receptors expressed on tumor cells and their ligands in target organs. Tumor cells use this mechanism to enter the microenvironment. Secondly, matrix-derived CXCL12 itself can stimulate the survival and growth of tumor cells in paracrine manner. Finally, CXCL12 promotes tumor angiogenesis by attracting endothelial cells into the tumor microenvironment. Therefore, antagonists targeting CXCR4 have become a promising method for the treatment of CXCR4-expressing tumors. By targeting the CXCR4/CXCL12 axis, CXCR4 antagonists block signals that cancer cells interact with the matrix for survival and drug resistance, mobilizing tumor cells from tissue sites, such as bone marrow, into the bloodstream. Also, it blocks the migration and dissemination of tumor cells in the process of tumor metastasis, making the tumor cells more sensitive to traditional treatments. Ulocuplumab is an oral drug targeting CXCR4 to inhibit tumor activity. After administration, the binding of ulocuplumab to CXCR4 destroys the binding of SDF-1 to CXCR4 receptor and subsequent activation of the receptor, which may inhibit the proliferation and migration of tumor cells.

Fig 1. Mechanism of Action of Ulocuplumab

Table 1. Clinical Projects of Ulocuplumab*

What We Provide

Therapeutic Antibody

Ulocuplumab

We provide high-quality Ulocuplumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=ulocuplumab

For research use only. Not intended for any clinical use.