Team:NCTU Formosa/Description

Description

The APOllO E.Cotector

This year, APOllO introduced a customized detecting platform - The APOllO E.Cotector.

Our customers can spontaneously choose from our biobrick libraries and match various plasmids for co-transformation. With this procedure, it not only helps us tailor our product to the wishes of our customers, but also brings us a major advantage in our manufacturing procedure. The simple process of co-transformation can create a dual display system that replaces the process of ligating several insertion genes into one single lengthy plasmid, which tremendously increases our manufacturing efficiency.

Our biobrick libraries consist of three kinds of plasmids: (1) scFv probes detect the target we want, (2) color signals are for observation, and (3) GBP can connect to gold. Once customers randomly select up to three plasmids, they can detect anything in the way they need it.

Single Chain Variable Fragment

ScFv is a fusion protein of the variable regions of heavy chain (VH) and light chain (VL) of immunoglobulins, and the heavy chain and light chain are connected with a short linker peptide of about 15 to 20 amino acids. Even with addition of a linker, scFv can still retain the complete function of antigen-binding site and specificity of the original immunoglobulin.



Figure 1. ScFv is a fusion protein of the variable regions of heavy chain(VH) and light chain(VL) of a monoclonal antibody

Moreover, scFv is only 20 percent of the size of normal antibody [4], so it can be easily produced and displayed by bacteria, such as E. coli, compared to monoclonal antibodies. In addition, scFv can be envisaged to be applied in the non-pharmaceutical sector, such as in food, cosmetic or environmental industries. The unique and highly specific antigen-binding ability might, for example, be exploited to block specific enzymes (e.g. enzymes that cause food spoilage) or to detect environmental factors present in very low concentrations (as biosensors)[2].



Figure 2. With scFv probes, E.Cotector could be applied to various fields. For example, health & medicine, food industry, agriculture, and environment.

Targeted drugs

We decided to focus on health and medicine and also found that the market for targeted drug is very significant. According to the statistics, the usage rate of targeted drug therapy has increased within ten years. In Figure 3, in 2003, targeted drug therapy is not commonly used, accounting for only 11% usage. Over one decade, it is estimated that the usage of targeted drug therapy dramatically will increase to 46%. Besides, targeted drugs show more accurate attack to cancer cells and less harmful damage to normal tissues [4] via specific binding to target molecules. Targeted therapy are alleged to be "personalized medicine" because health care professionals can use clinical test results from a patient to select a specific drug that has a higher likelihood of being effective for that particular person. This indicates detection for targeted drugs is a potential growing field and will become a prevalent pre-diagnosis for cancer treatment in the near future.



Figure 3. The usage of targeted drugs.

Pre-diagnosis of targeted drugs treatment

To create the new era of tailored targeted drugs, doctors must aim at appropriate target molecules for patients with particular diseases. In 2014, the U.S. Food and Drug Administration (FDA) issued a guideline to facilitate the development and review of diagnostics tests. The diagnostics tests are the steps to identify the abnormal cancer biomarkers. Moreover, the purpose of diagnostics tests are to help medical practitioners determine which patients could benefit from the certain drugs, conversely, those who should not receive the medication. If the treatment decisions is not optimal, it would not only cause the fatal body damage, but also lead to the waste of time, money and medical resources. FDA encourages the joint of targeted drugs therapies and precise diagnostics tests which are essential for the safe and effective use of targeted drugs[6].

The concept of combination therapy

Although targeted drugs treatments can lead to the dramatic regressions of solid tumors, the responses are often short-lived because resistant cancer cells arise after a period of treatment. The major strategy proposed for overcoming the resistance is combination therapy[7]. The clinical and preclinical researches further indicated that targeted drug therapy combined with another targeted drug therapy or other types of therapies to treat cancers simultaneously may attain greater effects than using only one therapy. With the concept of combination therapy, we can not only improve the treating effect but also reduce the occurrence of cancer cells resistance toward the targeted drugs as there are less probability that a single mutation will cause cross-resistance to both drugs[8].

Reference
 [1] Applications of single-chain variable fragment antibodies in therapeutics and diagnostics, Nina E. Weisser 1, J. Christopher Hall (2009)
[2] Stability Engineering of Antibody Single-chain Fv Fragments, Arne WoÈ rn and Andreas PluÈ ckthun (2001)
[3] From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. 1Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School (2008)
[4] From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. 1Division of Molecular Oncology, Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School (2008)
[5] Molecular-targeted agents combination therapy for cancer: Developments and potentials Feifei Li1,2,3, Changqi Zhao1,2 and Lili Wang3 Beijing Normal University, Beijing, China (2013)
[6]
[7] Evolutionary dynamics of cancer in response to targeted combination therapy Ivana Bozic, Johannes G Reiter, Benjamin Allen, Tibor Antal, Krishnendu Chatterjee,Preya Shah, Yo Sup Moon, Amin Yaqubie, Nicole Kelly, Dung T Le, Evan J Lipson, Paul BChapman, Luis A Diaz Jr, Bert Vogelstein, Martin A Nowak (2013)
[8] Personalized Cancer Treatment, Patient Resource


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