Mar 01, 2018
According to American Society of Clinical Oncology (ASCO), more women are diagnosed with breast cancer than any other cancer. Breast cancer is a form of cancer that starts with an abnormal growth of cells in the breast tissue. These cells usually form a tumor, that can be malignant, growing into surrounding tissues invading other distant areas of the body.
Generally, through a breast biopsy, the tissue is tested for hormone receptors and human epidermal growth factor receptor 2 (HER2). This HER2 gene controls the growth and repair of breast cells by producing HER2 proteins or receptors. But if there is an overexpression of HER2 gene, or the protein is over-expressed, the cells will grow uncontrollably and lead to HER2-positive breast cancer.
American Society of Clinical Oncology also declared that roughly 25 percent of all breast cancer cases is HER2-positive cancer. It is likely to be more aggressive form of breast cancer present in young women.
Trastuzumab is the first FDA-approved targeted treatment for HER2-positive since 1989. It is a monoclonal antibody that attaches to proteins or receptors on cancer cells to make the cells stop from growing and eventually die. Trastuzumab is effective in treating HER2-positive breast cancer. Due to its disadvantages like cost issues and tedious process of producing it, other drug manufacturers solve this problem by making a biobetter of trastuzumab. They invented a glycol-optimized monoclonal antibody made for better therapeutic outcome of breast cancer patients. This biobetter is an improvement to the originator biological molecule by modifying its molecular or chemical composition.
The improvement in this case is in the complex polysaccharide coating attached to the drug not in the drug itself. Glycosylation is an important process in the attachment of carbohydrate chains to the antibodies. Some proteins need to be glycosylated to fold correctly. Drugs need to be protected by glycosylation to avoid rapid degradation.
Antibody glycosylation is significantly influenced by the composition of the culture media. This include the concentration of ammonia, glutamine, glucose, and metal ions. It is important to measure N-glycan fucosylation at Asn 297 in the Fc domain for therapeutic antibodies whose mechanism of action includes antibody-dependent, cell-mediated cytotoxicity (ADDC). N-glycan fucosylation is well known to influence ADCC activity strongly.
ADDC occurs when an antibody binds to a cell-surface target antigen and recruits immune effector cells to lyse the target cell. A decrease in fucosylation at Asn 297 exhibits an increase in antibodies binding affinity to CD16 (Fc gamma receptor Illa) on natural killer cells and increase ADCC potency. (David Ho., et al, 2016).
One bioprocess technology institute successfully created fucose-free IgG1 antibodies. CRISPR-Cas9, a gene editing technique, was used to inactivate the key fucose-transporting gene (Slc35cl) in CHO cells to produce fucose-free antibodies. Researchers concluded that low fucosylation will increase therapeutic antibody efficacy and fucose-free antibodies have the potential to be used to treat breast cancer and leukemia.
Chinese hamster ovary (CHO) cell line is one of the most important cell lines used in the production of glycol-optimized monoclonal antibody. Traditionally, it can be cultured in suspension or cultured adherently to a carrier. Manufacturing process of the active ingredient starts with thawing and expanding the number of cells with a use of seed train and further proliferate in a bioreactor.
Esco VacciXcell offers a wide range of bioreactors that can produce high yields of monoclonal antibodies (mAbs) from hundreds of milligrams to grams. Commercially available, CelCradle™ bioreactor is the most advanced bioreactor to produce the targeted secreted products like mAbs. With the use of Tide Motion principle, the gentle vertical oscillation of culture medium and air provides cells an environment that is low shear stress to avoid cell damage or cell death. CHO cell cultures require high aeration and nutrition level to reproduce and perform more. This efficient nutrient and oxygen transfer is what allows the tide motion system to produce high-density cell yield.
As mentioned above, CHO cell line can be cultured adherently to a carrier. BioNOC™II is a 3D macrocarrier that ensures the cells being cultured are stable during and after culture. This macrocarrier is perfect for the anchorage of CHO cells during mAbs production. It provides high rate exposure of cells to aeration and culture medium because of its high porosity. Moreover, BioNOC™II is favorable for mAbs production because of its low fiber release that results in more downstream processes.
It is important that the process in mAbs production is linearly scalable due to the demand for treatment of breast cancer. The TideCell® is the world’s largest linearly scalable single-use bioreactor, from seed preparation to 5000 liters with closed automated cell harvesting. It is the pilot/production scale system of Esco VacciXcell’s Tide Motion Bioreactors which is perfect for the mass production of mAbs. As a result, bioprocessing time and costs for breast cancer treatment are greatly reduced.
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About HER2 Positive Breast Cancer
Breast cancers with HER2 gene amplification or HER2 protein overexpression are called HER2-positive in the pathology report. HER2-positive breast cancers tend to grow faster and are more likely to spread and come back compared to HER2-negative breast cancers.
Reference: Breast Cancer Organization. http://www.breastcancer.org
About Tide Motion Bioreactors
Tide Motion pertains to the gentle oscillation of culture medium into and out of the matrix vessel that intermittently exposes the cells to aeration and nutrition. The upward oscillation exposes the cells to nutrition, while the downward oscillation exposes the cells to aeration. At the same time, this process washes away products and wastes. This oscillation produces no air bubbles and low shear stress. View a range of products at http://www.vaccixcell.com/tide-technology/
About Esco VacciXcell
Esco VacciXcell is the bioprocessing division of Esco Group of Companies that specializes in the marketing and manufacturing of bioprocessing equipment for cell culture.
Esco VacciXcell provides turnkey manufacturing solutions using its proprietary Tide Motion™ technology to help developing nations to be self-sufficient in the manufacturing, storing, distribution, and administration of vaccines and other biologics, thus providing a complete solution from Discovery to Delivery. For more information on VacciXcell, please visit www.vaccixcell.com.