CCL2 Specific Neutra™ Antibody Products

Product list

CCL2 (Chemokine (C-C motif) ligand 2, also named GDCF-2, MCP-1, etc.) is a 13 kDa small cytokine (76 aa), predominantly secreted by monocytes, dendritic cells, and macrophages. Belonging to the CC chemokine family, CCL2 is an important regulator in the immune response, participating in the migration and infiltration of different types of cells such as memory T lymphocytes, monocytes, and NK cells. CCL2 is also closely related to cellular mechanics in inflammation, and the signal axis formed by CCL2 and its receptor CCR2 plays critical roles in the pathogenesis of various tumors, implicated in their initiation and progression. As a therapeutic agent, anti-CCL2 neutralizing antibody has important implications for translating CCL2 targeting to the clinical trials.

Its Gene ID: 6347, UniProtKB ID: P13500, and OMIM ID: 158105.

Fig.1 Chemokines participate in crosstalk between tumor cells and pro-inflammatory factors in the tumor microenvironment.¹

CCL2-CCR2 Signaling Axis

CCL2 mainly binds to its primary receptor, CCR2, forming a CCL2-CCR2 signaling axis, which is involved with the occurrence and growth of various cancers, including prostate cancer, breast cancer, hepatocellular cancer, lung cancer, nasopharyngeal carcinoma pancreatic cancer, and renal cancer. The signaling axis activates a string of signals, like PI3K/AKT, JAK/STAT, and p38MAPK, thus mobilizing downstream genes and transcription factors, leading to increased CCL2 expression and triggering activities of tumor cells. Besides, the CCL2-CCR2 axis can directly or indirectly modulate pathological angiogenesis. It also partakes in the invasion, abscission, and migration of cancer cells, thus modulating tumor metastasis.

Fig.2 The CCL2-CCR2 axis and transduction pathway.²

Antibodies in CCL2-Targeting Therapy

Inhibition of CCL2 by Monoclonal Antibodies

Based on the assumption that CCL2-neutralizing antibodies can bind to CCL2 and block the recruitment and differentiation of macrophages, there are many preclinical studies and clinical trials on CCL2-targeting therapy being conducted.

In a preclinical trial, it is demonstrated that a rat/mouse chimeric monoclonal antibody specifically neutralizes CCL2, and significantly reduces CD11b⁺CD45⁺ TAMs and CD11b⁺Gr1⁺ MDSCs, thus down-regulating tumor proliferation and prolonging the life expectancy of glioma-bearing mice. Another human anti-CCL2 antibody is reported to inhibit PC-3 cell proliferation and migration in vitro, and exhibits a broad spectrum of preclinical anticancer activity.

Combined Therapy

Considering the essential roles of the CCL2-CCR2 axis in cancers, CCL2-CCR2-associated targeted therapy has attracted increasing attention, and encouraging results have been reported in preclinical studies and clinical trials. Targeting CCR2 can be utilized as compensation for the limitation of targeting CCL2. In addition, as previous studies have also revealed that the CCL2-CCR2 signaling axis could induce tumor immune evasion via PD-1 signaling pathway, it has been proven that the combined treatment of inhibiting the CCL2-CCR2 axis is more effective than monotherapy.

Furthermore, it is reported that combined therapy of CCL2-neutralizing antibody along with anticancer vaccine increases the number of CD8⁺ T-cells and reduces tumor volume, indicating a promising strategy for cancer treatment.

Creative Biolabs offers many different anti-CCL2 antibody products. These antibodies are recombinantly expressed and could be used for various purposes. Customization of CCL2-based monoclonal antibodies or neutralizing antibodies is also available for you here.

REFERENCES

Hao, Qiongyu, Jaydutt V. Vadgama, and Piwen Wang. "CCL2/CCR2 signaling in cancer pathogenesis." Cell communication and signaling 18 (2020): 1-13.
Xu, Maosen, et al. "Role of the CCL2‐CCR2 signaling axis in cancer: mechanisms and therapeutic targeting." Cell proliferation 54.10 (2021): e13115.

Show More Close