CCR5 Antibodies

C-C chemokine receptor type 5 (CCR5)

Receptor for a number of inflammatory CC-chemokines such as CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation.

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Gene Information

Human
Gene Name:	CCR5
Uniprot:	P51681
Entrez:	1234

Family

Belongs to:
G-protein coupled receptor 1 family

Alternative Names

C-C CKR-5; C-C motif chemokine receptor 5 A159A; CCCKR5; CC-CKR-5FLJ78003; CCR5; CCR-5; CD195 antigen; CD195; chemokine (C-C motif) receptor 5; chemokine receptor CCR5; chemr13; CKR5; CKR-5; HIV-1 fusion coreceptor; IDDM22CMKBR5C-C chemokine receptor type 5

Molecular Weight

Mass (kDA):
40.524 kDA

Genomic Context

Human
Location:	3p21.31
Sequence:	3; NC_000003.12 (46370142..46376206)

Tissue Specificity

Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung.

Subcellular Localizations

Cell membrane; Multi-pass membrane protein.

Diseases

• Hiv Infections
• Immunologic Deficiency Syndromes
• Acquired Immunodeficiency Syndrome
• Cholangiocarcinoma
• Inflammation
• Virus Diseases
• Infective Disorder
• Neoplasms
• Malignant Neoplasms
• Simian Acquired Immunodeficiency Syndrome
• Nervousness
• Autoimmune Reaction

• Tissue Adhesions
• Arthritis
• Hepatitis
• Viremia
• Multiple Sclerosis
• Sclerosis

Interacting Proteins

• CCL17
• CCL4
• CCL5
• CD4
• CXCR4

Pathways

• Pathogenesis
• Tropism
• Chemotaxis
• Immune Response
• Viral Replication
• Secretion
• Cell Migration
• Membrane Fusion
• Cell Activation
• Cytokine Production
• Inflammatory Response
• Glycosylation
• Drug Resistance

• Reverse Transcription
• Cell Proliferation
• Localization
• Cell Death
• Chemokine Production
• T Cell Activation
• Endocytosis

PTMs

• Phosphorylation
• Glycosylation
• Cleavage
• Methylation
• Biotinylation
• Palmitoylation
• Hydroxylation
• Dephosphorylation
• Reduction
• Oxidation

• Deamination
• Acetylation
• Demethylation
• Formylation
• Ubiquitination
• Deglycosylation
• Sulphation
• Carboxylation
• Amidation
• Citrullination

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/CCR5

Best Uses Of The CCR5 Marker

This article will discuss anti CCR5 antibodies, CCR5 chemokine ligands, and their role in immunotherapy. This article will also look at the polymerization of CCR5.

Anti-CCR5 antibodies

Humanized monoclonal antibodies that are humanized against CCR5 has been developed to compete with HIV in binding to its receptor. These highly targeted proteins are efficient in protecting against HIV infection and minimizing adverse effects. In addition, they possess a long plasma half-life. These antibodies could have a wider therapeutic window and a wider range of antiviral effects than HIV-inhibitors drugs.

In the meantime studies of anti-CCR5 antibodies have shown that the majority of known alanine residues are necessary to replicate HIV-1. Antibodies that target the membrane-proximal region of CCR5 are effective against both CCR5-tropic as well as CXCR4 -tropic infections. CCR5-targeting antibody are therefore promising for future clinical trials.

The method used to identify the alanine residues implicated in viral infection was to use alanine scanning mutagenesis. These experiments revealed that no single-residue mutations had any effect on the degree of CCR5 expression on the cell surface. Some mutations, however, led to an increase in viral infections. N24A, for example, increased the rate at which it binds 50% while I23A increased its sensitivity by doubling. The MPR mutation was found in the SF162 strain.

These antibodies do not only possess anti-CCR5 function, but also stop the replication of viruses. The results revealed that anti-CCR5 antibodies did nothing to hinder immune function , and the subjects remained healthy, even after receiving these treatments. This is further evidence against the theory that CCR5 is an autoimmune target. These antibodies don't appear have any effect on immune function in many cases.

CCR5 chemokine CCR5 ligands

The creation of CCR5 chemokine lignds for human use is the next step in the fight against HIV. Chemokines have effects on disease that have been proven in animal models. These chemokine-ligands also have a high affinity to the CCR5 of human.

CCR5 acts as a costimulatory molecular that orchestrates the cell immune response, which is independent of the chemotactic. It stimulates the expression of activation markers in primary T cells, increases the proliferative response in response to antigens and sustains the re-admission of CD8+ T cells to dendritic cell.

The CCR5 molecule contains the D32 allele. This mutation is fairly recent and is highly prevalent. It also has an identifiable geographic distribution. This suggests that there is positive selection. However, it would take an estimated 127,500 years to be present in 10% of the population. Additionally, genetic recombination rates put the age of the mutation between 1000 and 2000 years. It is therefore crucial to look into the genetic background of the ligand prior to consummating it.

HIV attaches to CD4 by binding the gp120 viral protein. The gp120 viral protein binds to the CCR5 receptor via the second extracellular loop. These natural CCR5 binding ligands also compete with HIV binding. Monoclonal antibodies can also be used to oligomerize CCR5 ligands.

CCR5-resistant mutations within the env gene have no effect on the efficacy or safety of antiviral strategies. CCR5 ligands have also been found to trigger the shift in the phenotypes of HIV. This makes it easier to HIV chemokine therapy to be efficient. Despite the fact that antiviral drugs have not been successful in the past 10 years, there is hope for the future.

CCR5 immunotherapy

Researchers have discovered a new mechanism that stimulates the reactivation and activation of tumor-specific T cells in mice. These cells are reprogrammed to reduce the growth of tumors and to escape negative selection. These findings suggest that CCR5 is a key factor in activating these immune cells. Further, CCR5 has been linked to increased tumor immunity which could explain the differences between acute and chronic immune responses.

While combined antiretroviral therapy (CART) can reduce HIV-1 replication, it does not eradicate latent reservoirs of the virus, which remain in healthy individuals. It also can cause side effects. To overcome these issues antigen-based therapies have been proposed as an alternative. Anti-CCR5 antibody therapies have been developed to replace CART. This treatment could be able to stop the transmission of HIV-1 between humans and mice.

Researchers have identified the chemicals CCR5 and CXCR5. Both chemicals regulate leukocyte trafficking and play a vital role in the immune system. The CCR7/CCL19-21 pair regulates the interaction of the naive T cell with mature antigen-presenting cells in lymph nodes. Inflammatory chemicals lead lymphocytes that have been activated to tissues in the peripheral region where they can aid in healing and eradication of tumors.

The anti-cancer antibody anti-CCR5 is a potent anti-cancer drug approved for treatment of various kinds of cancers. Numerous clinical trials have revealed promising results for Boster Bio CCR5 immunotherapy. While the results are not conclusive, they could be beneficial to patients with a variety of inflammation-related diseases and autoimmune disorders. The company is hoping to offer this treatment in the clinic in the near future.

CCR5 polymerization

Research into cardiovascular disease is revealing the importance of CCR5 markers. While chemokines and receptors and chemokines are crucial in the prevention and treatment of vascular diseases but there are still a lot of questions about the role of CCR5 as a factor in atherosclerosis. This study investigated the effects of the CCR5 mutation (CCR5-del32) on inflammation in the system and the thickness of the intimamedia. The cardiovascular disease indexes of patients with CCR5–del32 mutations were also examined by researchers.

While the CCR5 D32 allele is only a recent discovery its geographic distribution and frequency suggest that it has a recent source and positive selection. To attain a 10% population frequency one mutation could require around 127.500 years. This timeframe is consistent with the estimates of genetic recombination as well as mutation rates. These numbers aren't perfect, however they provide a clear picture about the evolution of CCR5 markers.

While there is a lot to be learned about the role CCR5 plays in cell immunity and function, the main function of CCR5 is the activation of effector reactions. CCR5 ligands can increase the activity of APC and T cells. The CCR5 receptor, a vital component of chemokines, increases the immune response of T cell cells in the body. This receptor is not utilized for cancer immunotherapy or recombinantDNA delivery.

The future role of agents targeting CCR5 is unclear. More research is needed to define the function of CCR5 in the progress of the HIV-1 disease. If the studies are successful will open the doors to new CCR5-targeted HIV therapies. CCR5's future is bright. CCR5 could be a crucial factor in the development of more efficient HIV therapies in this age of personalized medicine.

Drugs that target CCR5

The development of drug candidates to treat cancer has begun with the identification of new mutations in the CCR5 receptor. These mutations were chosen based on previously published phenotypes. This included two previously identified antibodies, 3A9, and 2D7 which recognized the amino-terminal domains of CCR5. Two additional mutations that were identified in this study were G286F and L203F, which required multiple chemokine receptors to recognize them.

These drugs block fusion by targeting the receptor at the cell surface. Maraviroc and Aplaviroc both block the fusion process. Nonlinear regression is the mechanism through which the two agonists block the signal. The potency of these drugs is expressed in fold changes compared to WT CCR5.

There are a myriad of mechanisms of action for the molecules in the pipeline. Chemokines compete with CCR5 for binding to gp120. The chemokine blocks the receptor from internalizing, resulting in a steady decrease in the number of HIV-positive cells in the body. It isn't clear what role each CCR5 ligand plays to HIV inhibition. They do possess antiviral properties, and they are associated with strong psychokinetic effects.

The surface expression of all CCR5 mutants were similar in TAK652 which suggests that they could be transformed into antagonists. This is due to bias that could be introduced into their use. Drugs that target CCR5 are available from Boster Bio