Domesticated cancer treatment using a nanometer drug carrier: the future is here

The use of monoclonal antibodies to target antigens expressed in the cancer tumor is an effective tool for the diagnosis and treatment of cancer, autoimmune diseases and inflammatory diseases

The author: Dr. Usherat Frankel, Research Director at Imion Pharma, which develops technology for domesticated cancer treatment
The use of monoclonal antibodies to target antigens expressed in the cancer tumor is an effective tool for the diagnosis and treatment of cancer, autoimmune diseases and inflammatory diseases. Today it is already known that the effectiveness of cancer treatment is increased by a combination of an antibody and a chemotherapeutic drug. But the use of chemotherapeutic drugs involves side effects that may limit the treatment in light of the lack of specificity of these drugs.
One way to improve the efficiency of antibodies is their coupling to toxin molecules, which damage the cell skeleton (microtubule disrupting agents). In August 2011, the American Food and Drug Administration (FDA) approved a drug called Adcetris, which was developed by Seattle Genetics for the treatment of certain types of lipoma and is actually based on this technology known as Antibody Drug Conjugates (ADC). The technology was published in the American scientific and popular press, including the New York Times and the Wall Street Journal as a revolution in patient care and the pharmaceutical market. However, the use of chemotherapeutic drugs that are not toxins that work with a different mechanism of action is currently not possible with the ADC technology. The ability to attach only a small number of drug molecules to the antibody as well as the inability to use a combination of several drugs constitutes a limitation to the therapeutic applications of the technology.

At this point, the Nanomabs platform, the fruit of Israeli research development, comes into the picture. It is a platform for the domesticated transfer of a cancer drug or combination of drugs used primarily in the treatment of solid, aggressive and difficult-to-treat cancers. Controlled transfer of the drug molecules specific to the tumor area and even into the cancer cell is done by entrapping the drug or the drug combination inside a polymeric nanoparticle. This particle is domesticated as a kind of guided missile to the cancerous target cell by a specific interaction of an antibody that wraps the particle with an antigen that is more expressed in the cancerous cell. Therefore, it is possible to increase the effectiveness of the medicine due to a specific arrival into the tumor cell, as well as a reduction in the problematic side effect profile of the chemotherapeutic drugs due to a decrease in the exposure of healthy tissues to the drug molecules trapped inside the particle before they enter the cancer cell. This platform was developed by a team led by Professor Shimon Benita from the Institute of Drug Sciences at the School of Pharmacy at the Hebrew University. He was a partner in the research on the antibodies with Dr. Jean Kadosh, Vice President of Research and Innovation at Imion Pharma.

If so, what is the nanomab particle?
The technology is based on five basic modules:

1. A polymer particle about 100 nanometers in size. The particle contains the drug charge which is delivered directly to the cancer cell. The polymers from which the particle is made break down inside the cell.
2. A protective layer on the surface of the particle by a polymeric residue known as This PEG layer makes the particle stealthy against the cells of the immune system responsible for eliminating foreign substances from the body.
3.  A molecule that binds the antibody to the polymeric particle.
4. Anticancer drug or drugs. The drugs are trapped inside the polymer particle and in fact do not come out of it until the particle breaks down inside the cell. A number of anticancer drugs with different mechanisms of action have been successfully entrapped inside the nanoparticle. The possibility of administering a combination of drugs expands the possibility of treatment.
5. Monoclonal antibody. The main function of the antibody is its use for the purposes of homing the particle to the cancer cell.

If so, the question arises, what is the mechanism of action?
The purpose of using NanomAbs is actually to increase the specificity of the drug in order to improve the efficiency and safety of the chemotherapy. The use of a unique linker molecule to conjugate a controlled number of antibodies to a stealthy polymeric particle containing the drug was found to be effective. The NanomAbs technology showed an improvement in the efficiency of transferring a chemotherapeutic drug into a cancer cell which is usually not accessible at a sufficient level while reducing the elimination of the drug by organs such as the liver, spleen, kidneys. Indeed, when comparing the effectiveness of the NanomAbs containing the chemotherapeutic drug Taxol compared to the conventional drug, an improvement in the anticancer effect is indeed seen both in cell culture models and in models of lung and prostate cancer in mice.
After systemic administration by injection, the NanomAbs accumulate in the cancer tissue because the walls of the blood vessels in the tumor tissue are perforated and allow the passage of particles with a size of about 100 nanometers. The accumulation of the particles in the tissue by passing through the walls of the blood vessels as a sort of sieve allows for a specific interaction of the antibody with an antigen found on the surface of the cancer cell. The interaction between the antibody on the surface of the particle and the antigen on the surface of the cell can be simulated as the interaction of a key with a lock. The link allows the entry of the particle into the cell in a process that can be likened to a kind of swallowing action of the cell (endocytosis). The ingested particle is digested inside the cell, which actually releases the drug molecules trapped in the particle in a controlled manner and are the ones that cause the death of the cancer cell.

The injectable applications of the technology have been commercialized through an application company for Immune Pharmaceuticals, which is currently preparing for clinical trials. Since research and development work has already been done to create a freeze-dried powder formulation that has shown stability for two years, the road to a relatively quick commercialization of the drug is already paved. Imion's vision is that at the end of the clinical development and approval process, this technology will open up new treatment possibilities for cancer patients while improving the efficiency and safety of the treatment. Last week, the Imion company announced a merger with an American pharmaceutical company traded on the over-the-counter (OTC) drug exchange.

Additional publications

A quantitative evaluation of the molecular binding affinity between a monoclonal antibody conjugated to a nanoparticle and an antigen by surface plasmon resonance.
Debotton N, Zer H, Parnes M, Harush-Frenkel O, Kadouche J, Benita S.
Eur J Pharm Biopharm. 2010 Feb;74(2):148-56. Epub 2009 Oct 14.
http://www.ncbi.nlm.nih.gov/pubmed/19835957
Overcoming the formulation obstacles towards targeted chemotherapy: in vitro and in vivo evaluation of cytotoxic drug loaded immunonanoparticles.
Debotton N, Parnes M, Kadouche J, Benita S.
J Control Release. 2008 May 8;127(3):219-30. Epub 2008 Feb 8.
http://www.ncbi.nlm.nih.gov/pubmed/18343522
The design and evaluation of a novel targeted drug delivery system using cationic emulsion-antibody conjugates.
Goldstein D, Nassar T, Lambert G, Kadouche J, Benita S.
J Control Release. 2005 Nov 28;108(2-3):418-32. Epub 2005 Oct 13.
http://www.ncbi.nlm.nih.gov/pubmed/16226821
The ligand nanoparticle conjugation approach for targeted cancer therapy.
Karra N, Benita S.
Curr Drug Metab. 2012 Jan; 13 (1): 22-41 21892918
http://lib.bioinfo.pl/auid:18550854