Plerixafor (Mozobil)

My opinion:

Plerixafor works against the part of immune system (M2macrophages) that helps the tumor to regrow after an effective treatment has succeeded to kill part of it. Therefore, Plerixafor is a great supportive treatment for any effective anti cancer strategy including surgery, chemo and radiotherapy.

We do not have any experience with it.

Summary & Mechanism

The immune system plays a major role in cancer progression. In solid tumors, 5-40 % of the tumor mass consists of tumor-associated macrophages (TAMs) and there is usually a correlation between the number of TAMs and poor prognosis, depending on the tumortype. TAMs usually resemble M2 macrophages. Unlike M1-macrophages which have pro-inflammatory and anti-cancer functions, M2macrophages are immunosuppressive, contribute to the matrix-remodeling, and hence favor tumor growth. (Ref.)

Indeed, macrophages are a type of white blood cells and are often found in two forms in the body: M1 macrophages, which protect against infection and can work to destroy tumours, and M2 macrophages which promote wound-healing and have been linked to tumour growth and spread. Cancer-killing action of effective treatments (such as 3BP or Salinomycin) can trigger a process of wound-healing, where white blood cells (M2 macrophages) cluster around blood vessels damaged by the anti-tumor treatments. These M2 macrophages cells, repair tissue damage and build new blood vessels, a process that will help the tumor to grow again after treatment (the anti-inflammatory types of macrophages, known under the generic term M2 are induced by anti-inflammatory mediators, including IL-4, IL-10, TGF-β and M-CSF (Ref.))

It has been recently shown that using a drug to stop these repair cells from working, may inhibit the fast regrowth of tumors. (Ref1, Ref2) This drug is Plerixafor a alpha chemokine receptor CXCR4 antagonist.

Plerixafor was approved in 2009 under the name Mozobil (Ref.) Also used as HIV treatment.

May be effective against Cancer Stem Cells in RCC (but others as well) http://www.ncbi.nlm.nih.gov/pubmed/23630186

Safety/Toxicity

Side effects are limited: Nausea, diarrhea and local reactions were observed in over 10% of patients. Other problems with digestion and general symptoms like dizziness, headache, and muscular pain are also relatively common; they were found in more than 1% of patients. Allergies occur in less than 1% of cases. Most adverse effects in clinical trials were mild and transient. (Ref)

Indications and usage: http://products.sanofi.us/Mozobil/mozobil.html

Preparation & Administration

Plerixafor is absorbed quickly and peak concentrations are reached after 30 to 60 minutes. Half life is 3 to 5 hours. Excreted via the kidneys, with 70% of the drug being excreted within 24 hours.

Mozobil (plerixafor injection) is provided as a 20 mg/mL solution in a single use vial.
(Each vial is filled to deliver a volume of 1.2 mL and contains 24 mg of drug and 5.9 mg sodium chloride dissolved in water for injection adjusted to a pH of 6.0-7.5 with hydrochloric acid and with sodium hydroxide, if required.) (Ref.)

The recommended dose of Mozobil is 0.24 mg/kg of actual body weight, administered by subcutaneous (SC) injection. (Ref.)

It should be probably administrate just before, during, or just after an effective anti cancer treatment and possibly a few days after to inhibit reconstruction of veins by M2 macrophages.

Source & Cost

Plerixafor is a white to off-white crystalline solid. It is supplied as a clear, colorless to pale yellow, sterile, preservative-free, isotonic solution for subcutaneous injection. The issue is that one ready made injection of 24mg costs about 7000 euro.

However, it can be available at companies such as Sigma at a much lower price, i.e. about 200 euro for about 25mg of powder.

When searching for suppliers here are various names of the same: Plerixafor, Mozobil, AMD 3100, JM 3100, SDZ SID 791. CAS No: 110078-46-1 Here is the price at Sigma, but others are cheaper.

Synergists & Antagonists

It could be used together with effective anti cancer treatments such as 3BP, Salinomycin and even during effective chemo treatments, next to added antiangiogenesis supplements and/or drugs.

Relevant literature

Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

Tumour cell derived effects on monocyte/macrophage polarization and function and modulatory potential of Viscum album lipophilic extract in vitro

Human breast cancer cells educate macrophages toward the M2 activation status

Tumor-associated macrophages in breast cancer: distinct subsets, distinct functions

Much More than M1 and M2 Macrophages, There are also CD169(+) and TCR(+) Macrophages

CXC chemokine receptor 4 is essential for maintenance of renal cell carcinoma-initiating cells and predicts metastasis In conclusion, CXCR4 identifies a subpopulation of tumor-initiating cells in RCC cell lines and plays a role in their maintenance. The relative insensitivity of such cells to tyrosine kinase inhibitors might contribute to the development of therapy resistance in RCC patients. Future therapies therefore could combine blockade of the CXCR4 signaling pathway with standard therapies for more effective treatments of metastatic RCC.

A double agent in cancer: Stopping macrophages wounds tumors

Great discussion on M1 and M2 http://journal.frontiersin.org/article/10.3389/fimmu.2015.00212/full#F1

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

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Fred
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Fred

Daniel, have you initiated Plerixafor therapy yet?