CCR5 Specific Neutra™ Antibody Products

CCR5, also known as the C-C chemokine receptor type 5, is a vital protein on white blood cells that mediates immune system responses by directing immune cell migration to inflammation sites. Crucially, CCR5 serves as a co-receptor for HIV-1, making it significant in HIV therapeutic strategies and vaccine development. The receptor interacts with chemokines like RANTES (CCL5), MIP-1α (CCL3), and MIP-1β (CCL4), which are essential for immune cell activation and migration. The presence of genetic variants such as the CCR5-Δ32 mutation can provide resistance to HIV. Research into CCR5's role in autoimmune diseases and allergies also shows its potential as a therapeutic target, not only in managing HIV but also in treating various inflammatory and autoimmune conditions.

Its Gene ID: 1234, UniProtKB ID: P51681, OMIM ID: 601373

Signal Pathway of CCL5/CCR5 Axis

Binding of CCL5 to CCR5 activates various downstream pathways including PI3K/AKT, NF-κB, HIF-α, and others. This leads to cellular responses such as cell proliferation, migration, apoptosis, and immune responses.

• CCL5/CCR5 axis in PI3K/AKT pathways
  CCL5/CCR5 activates PI3K/AKT, leading to phosphorylation and activation of downstream proteins such as AKT and GSK-3b, which are involved in cell survival, proliferation, and apoptosis.

Fig.1 CCL5/CCR5 axis in PI3K/AKT pathways.¹

• CCL5/CCR5 axis in HIF-α pathway

The interaction of CCL5/CCR5 can stabilize and increase HIF-1α under hypoxic conditions, enhancing angiogenesis and cellular adaptation to low oxygen levels through the regulation of genes involved in these processes.

Fig.2 CCL5/CCR5 axis in HIF-α pathway.¹

• CCL5/CCR5 axis in NF-κB pathway
  CCL5/CCR5 activation results in the phosphorylation of NF-κB pathway components, promoting the transcription of genes associated with inflammation, immune response, and cell survival.

Fig.3 CCL5/CCR5 axis in NF-κB pathway.¹

CCL5/CCR5 Pathology

The CCL5/CCR5 signaling axis influences various pathological processes across inflammatory diseases, viral infections, and cancer, showcasing its critical function in immune response modulation and disease progression.

• Inflammatory Diseases

CCL5/CCR5 significantly impacts inflammatory diseases by directing the migration and accumulation of immune cells at inflammation sites, exacerbating conditions such as atherosclerosis and rheumatoid arthritis. This axis promotes chronic inflammation and tissue damage.

• Viral Infections

For viral infections, notably HIV, CCL5/CCR5 acts as a crucial co-receptor for virus entry into cells. It's targeted by anti-HIV therapies to block this entry, and similar mechanisms are suggested in the context of severe COVID-19, indicating a broader role in viral pathogenesis.

• Cancer

In cancer, CCL5/CCR5 facilitates tumor progression by enhancing inflammation, tumor cell migration, invasion, and metastasis. It also modifies the tumor microenvironment to favor tumor growth and helps tumors evade immune surveillance, significantly impacting breast, gastric, and other cancers.

Treatment targeting CCL5/CCR5

Strategies targeting the CCL5/CCR5 axis are primarily centered around the development of inhibitors that block the interaction between CCL5 and CCR5, aiming to mitigate the pathological effects mediated by this signaling pathway.

• Small Molecule Inhibitors: A prominent approach involves the use of small molecule inhibitors such as Maraviroc and Cenicriviroc. Maraviroc, initially approved for HIV treatment, functions by blocking CCR5 and preventing the virus from entering cells. This drug is also being explored for its potential in cancer therapy by inhibiting the migration of cancer cells and reducing tumor growth. Cenicriviroc, another CCR5 inhibitor, has broader implications due to its dual inhibition of CCR2 and CCR5, making it effective in treating conditions like non-alcoholic steatohepatitis (NASH) by reducing inflammation and fibrosis.
• Monoclonal Antibodies: Monoclonal antibodies targeting CCR5 are another therapeutic strategy. These antibodies can block CCR5 function and are being investigated for their efficacy in reducing inflammation and controlling the progression of diseases mediated by excessive CCR5 activity.
• Gene Therapy: Gene therapy approaches aim to disrupt CCR5 expression in cells, particularly in the context of HIV. By knocking out the CCR5 gene using technologies like CRISPR, researchers aim to render cells resistant to HIV infection, a strategy that has shown promise in clinical trials.
• Combination Therapies: Combining CCR5 inhibitors with other treatments, such as chemotherapeutic agents, has the potential to enhance therapeutic efficacy. For example, combining Maraviroc with chemotherapy could potentiate anti-tumor effects by not only inhibiting tumor cell migration but also reducing the tumor's ability to evade the immune system.

Creative Biolabs is committed to providing our clients with the finest and most comprehensive one-stop services and products related to C-C motif chemokine receptor 5 (CCR5). With our cutting-edge neutralizing antibody and recombinant antibody technology platform, we have confidence in delivering top-quality service.

REFERENCE

1. Zeng, Zhen, et al. "CCL5/CCR5 axis in human diseases and related treatments." Genes & diseases 9.1 (2022): 12-27.