Next-IO™ Anti-CCL2/CCR2 Axis Targeted Therapeutic Antibody Program

About This Program

This program aims to develop anti-CCL2/CCR2 axis targeted therapeutic antibody for immuno-oncology.

Chemokines are important regulators driving tumor development. CCL2, also known as monocyte chemotactic protein-1, is an effective chemokine for the recruitment of TAM. Cumulative studies have shown that CCL2 promotes the recruitment of TAM by activating its receptor CCR2 during tumor invasion and metastasis. Recent studies have shown that the CCL2 / CCR2 axis is responsible for the M2 polarization of TAM, thus forming a tumor support environment. A growing number of preclinical studies have shown that targeting TAM by blocking the CCL2 / CCR2 axis inhibits tumor progression and may be a potential therapeutic target for several malignancies.

CCL2/CCR2 Axis

CCL2 is secreted by cancer cells and surrounding stromal cells, including endothelial cells, fibroblasts, monocytes, and cancer cells. CCR2 is expressed at high levels in inflammatory monocytes, dendritic cells, and natural killer cells and at low levels in neutrophils and T and B lymphocytes. Binding of CCL2 to the G protein-coupled receptor CCR2 triggers intracellular signaling in cancer and other cell types. The published highlights are as follows:

CCL2-CCR2 signaling promotes cancer cell proliferation and survival, induces cancer cell migration and invasion, stimulates inflammation and angiogenesis to promote cancer progression.
CCL2 also induces the expression of MMP2 and MMP9 in cancer cells, both of which promote cancer cell invasion.
TAM and MDSC recruited by CCL2 trigger angiogenesis switches and inhibit immune-mediated cancer cell attack.

Fig.1 Role of CCL2‐CCR2 signaling in cancer progression.¹

CCL2/CCR2 Axis in Cancer Studies

The targeting of the CCL2/CCR2 Axis-Targeted / Fas system in therapeutic strategies is particularly complex, due to the intricate signal path interaction with other molecules. Here are some published data about CCL2/CCR2 AXIS-TARGETED work as a potential target for cancer immunotherapy.

SACC patients with high CCL2 expression were significantly worse than those with the low CCL2 expression.

Fig.2 The overall survival rate and the disease free survival rate of SACC patients with different expression level of CCL2 and CCR2.²

The CCR2 antagonist attenuated the infiltration of TAMs and the tumorigenicity of SACC cells.

Fig.3 Analysis of the weekly tumor volumes and gross observation of the harvested tumor tissues after 4 weeks.²

CCL2/CCR2 blockade inhibits the growth of CCL2-overexpressing tumors.

Fig.4 Tumour volumes of Hepa1-6 and LPC-H12 tumor in C57BL/6 mice were measured in indicated treatment groups.³

Ongoing Clinical Trials

Currently, several anti-CCL2/CCR2 antibodies are currently being evaluated in clinical trials after successful testing in animal models. An increasing number of therapeutic molecules are getting confirmed on its role in immune responses and early clinical trial data shows great promise. However, further studies are needed to optimize the efficacy, safety, and combination strategies to achieve greater clinical success.
In this case, CCL2/CCR2 axis is still a compelling target for cancer immunotherapy.

Program Plan

We have extensive knowledge of end-to-end program development. For each program, we are committed to delivering the final complete program to our clients within 1.5 years prior to entering the IND stage.

Fig.5 Project pipeline management of therapeutic monoclonal antibody.

Cooperation

Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop anti-CCL2/CCR2 axis targeted therapeutic antibody program together. Our scientists are dedicated to bringing together years of valuable experience to our partner and achieve a meaningful partnership. For commercial partners interested in our Next-IO™ programs, Creative Biolabs welcomes collaboration. Here are two ways for your choice, and please contact us for more details.

1) Collaborate with us and co-develop the programs from discovery phase to IND enabling. Costs will be shared.

2) Become a licensed candidate of our programs.

With our quality control protocol and knowledge of global regulatory requirements, we can help our partners and their programs enter the market faster. Look forward to cooperating with you in the near future.

References

Yumimoto, K.; et al. Potentials of C‐C motif chemokine 2–C‐C chemokine receptor type 2 blockers including propagermanium as anticancer agents. Cancer science. 2019, 110(7): 2090-2099.
Yang, Z.; et al. CCL2/CCR2 axis promotes the progression of salivary adenoid cystic carcinoma via recruiting and reprogramming the tumor-associated macrophages. Frontiers in oncology. 2019, 9: 231.
Li, X.; et al. Targeting of tumour-infiltrating macrophages via CCL2/CCR2 signalling as a therapeutic strategy against hepatocellular carcinoma. Gut. 2017, 66(1): 157-167.

For Research Use Only | Not For Clinical Use