Magic™ Humanized CCR2 Knock-In Mice

The tumor microenvironment is infiltrated by different immune cells, among which CC chemokine receptor 2 (CCR2)-positive macrophages play essential roles in tumor progression and metastasis. Targeting CCR2⁺ macrophages by utilizing anti-CCR2 inhibitors (small molecules and monoclonal antibodies) demonstrates a significantly promising response rate clinically in various cancer types. Creative Biolabs has successfully established an optimized Magic™ “humanized” animal platform to offer specialty manipulated CCR2 knock-in mice for our clients all over the world.

CCR2 Molecule

Tumor-associated macrophages (TAMs) have been evidenced to have the capability to suppress the immune activity and promote tumor growth. Targeting the predominant tumor-infiltrating TAMs is a favorable approach to reverse the immunosuppression in the tumor microenvironment and enhance anti-tumor immunity. To elucidate the mechanisms of immunosuppression induced by the TAMs, the signal pathways involving in the TAMs survival and function or specific expression patterns on TAMs have been widely explored.

CCR2, a member of the G protein-coupled receptor superfamily (GPCRSF) binds to its unique ligand “chemokine CCL2” which is synthesized by tumor and stromal cells. CCR2 resides on inflammatory monocytes which origin from bone marrow-derived myeloid cells. CCR2⁺ inflammatory monocytes infiltrate into the tumor microenvironment and differentiate to tumor-associated macrophages (TAMs). Blocking CCR2 could prevent TAMs accumulation and deplete TAMs in the tumor, thus enhancing anti-tumor immunity.

CCR2 Signal Pathway

Monocytes, including resident and inflammatory monocytes, are produced and stored in the bone marrow. The inflammatory monocytes have their dominant expression of CCR2 on the cell membrane. Under mobilization of CCL2/CCR2 signaling, CCR2⁺ inflammatory monocytes inflow from the bone marrow to the blood and finally, they are recruited to the primary tumor and premetastatic site where they differentiate into TAMs. CCR2⁺ TAMs possess important tumor-promoting properties: enhancing tumor growth, chemoresistance, and engineering immune evasion. Also, CCR2⁺ TAMs facilitate tumor cells metastasis from the primary tumor site to distant sites which significantly enhances malignancy. The blockade of the CCL2/CCR2 signal pathway using CCR2 inhibitors (small molecules and monoclonal antibodies) could reduce the number of tumor-infiltrating CCR2⁺ TAMs, thus providing an important approach for cancer intervention.

Fig.1 CCL2/CCR2 signaling in tumor metastasis. (Qian, 2011)

Development of Humanized CCR2 Knock-In Mice

CCR2 inhibitors reduced tumor regression in preclinical tumor models and its concomitant use with other therapeutics (such as chemotherapeutics) could augment their efficacy in clinical trials. Thus, the development of preclinical models for the evaluation of CCR2⁺ targeting candidates is crucial. With advanced technology, Creative Biolabs has successfully established an array of well-established Magic™ “humanized” animal models, especially for humanized CCR2 knock-in mice. Our scientists focused on humanized mouse models are pleased to assist you in your studies of anti-tumor immunotherapies. What’s more, we also established a comprehensive in vitro immunomodulation assessment service using various approaches. Please feel free to contact us or more details.