Difference between revisions of "Team:NCTU Formosa/Description"

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<div class="content"><h1>APOllO E.Cotector</h1>
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<div class="content"><h1>The APOllO E.Cotector</h1>
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<p>To enhance the efficiency of diagnosis and provide reference for proper usage of targeted drugs and combination therapy, we come up with the idea of detecting multimarker at the same time and this was how our marvelous E.Cotector was born. This year, NCTU_Formosa commits to creating a multimarker diagnosis platform via scFv as probes for helping physicians to determine and prescribe the usage of targeted drugs in cancer patients, especially the monoclonal-antibody-targeted drugs.</p></div>
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<p>This year, APOllO introduced a customized detecting platform - The APOllO E.Cotector.</p>
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<p> 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. </p>
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<p>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.</P>  
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<div class="content"><h1>Customized Detection Platform</h1>
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<div class="content"><h1>Single Chain Variable Fragment</h1>
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<p>This year, APOllO, introduce a revolution customized detecting platform. We call it the E.Cotector.</p>
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    <p>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. </p>
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<p>We built three individual biobrick libraries of scFv probes, color signals and Gold Binding Polypeptide (GBP) for the customized detection platform. Probes detect the target we want. Fluorescence protein or chromoprotein expresses signal for observation. GBP acts as a bridge to connect our product to gold, which enables our product to be applied to biosensors. Our customers can spontaneously choose from our libraries, pair up any biobricks. Next, comes the most crucial part of our project. Our team will then co-transform the plasmids into <i>E. coli</i>. Our customized detection platform, The APOllO E.Cotector, is therefore born.  By co-transforming plasmids, it not only helps us customize our product every which way for our customers but also brings us a major advantage in our manufacturing procedure. We no longer have to build lengthy biobricks, which tremendously increases our manufacturing efficiency.</P>  
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<img src="https://static.igem.org/mediawiki/2015/6/62/Design_Figure_2-2.png" height="200px"><br><br>
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Figure 1. ScFv is a fusion protein of the variable regions of heavy(VH) and light chain(VL) of a monoclonal antibody
 
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<p>Moreover, scFv is only 20 percent of the size of normal antibody <sup>[4]</sup>, so it can be easily produced and displayed by bacteria, such as <i>E. coli</i>, 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)<sup>[2]</sup>.</p>
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<h1>Single chain variable fragment as probe</h1>
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<p> In our product, we chose Single chain variable fragment (scFv) Abs as probes to detect. ScFv are one of the recombinant antibody (rAb) fragments, which are popular therapeutic alternatives to full length monoclonal Abs. Compared to generating whole Abs from animal cell culture, scFv are smaller and can be expressed rapidly, economically and in large quantities in a bacterial host, such as <i>E. coli</i>. A scFv possesses the complete antigen binding site, which contains the variable heavy (VH) and variable light domain of an antibody. The VH domain is linked to a VL domain by an introduced flexible polypeptide linker. A scFv is capable of binding to the target antigens with an affinity similar to that of the parent mAb. Since scFv fragments contain specific antigen binding units, scFv fragments show tremendous versatility and importance in human therapeutics and diagnostics.<sup>[1]</sup> In addition, scFv fragments 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), bacteria (e.g. in toothpaste or mouthwashes) or to detect environmental factors present in very low concentrations (as biosensors).<sup>[2]</sup></p>
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Figure 1.
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Figure 2. With scFv probes, E.Cotector could be applied to various fields. For example, health & medicine, food industry, agriculture, and environment.
 
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<div class="content"><h1>Health and Medical Detection Platform</h1>
 
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  <p>With our hit product, E.Cotector, we can focus on health and medical dimension. We want to provide a convenient and efficient diagnosis for prescribing personalized targeted drug therapy via tissue biopsies. Therefore, we chose single chain variable fragments (scFv), which are directly from monoclonal antibody targeted drugs to act as our probe to detect specific biomarkers. Our customer can pair up any scFv with any color signal. By changing various kinds of scFv on the surfaces of E.Cotector, it can identify multimarkers and suggest appropriate different kinds of targeted drugs.</P>
 
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  <p> Our E.Cotector can consequently bind to various targeted antigen also simultaneously express color as signal for instant observation. We provide another plasmid of Gold Binding Polypeptide for customers to pair up. By pairing up scFv and GBP, we can achieve quantitative detection through biosensors. In conclusion, the customized APOllO E.Cotector will bring a brand new era for pre-diagnosis target drugs treatment.</P>
 
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<div class="content"><h1>Properties and development of pre-diagnosis of targeted drugs</h1>
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<div class="content"><h1>Properties and development of targeted drugs</h1>
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<p> 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 <sup>[4]</sup> 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. </p>
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  <p>This year, we decided to utilize the scFv as probes to detect cancer markers and aid in the prescription of targeted drugs in cancer treatments. Targeted drugs therapy utilize compounds that are capable of inhibiting target molecules, the cancer markers which send messages along signaling pathways in cell growth, cell division or cell death.<sup>[3]</sup> Via specific binding to target molecules, targeted drugs show more accurate attack to cancer cells and less harmful damage to normal tissues. <sup>[4]</sup> The precision of targeting the cancer cells has enhanced the efficiency of treatment by a large margin. Targeted therapy is a major step forward for many cancers, especially advanced cancers, and physicians and researchers are now focusing on the development of targeted drugs, creating a new era of personalized cancer treatment. <sup>[5]</sup>Targeted therapy are so-called "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.</p>
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<h2>Pre-diagnosis of targeted drugs treatment</h2>
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  <p>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 guidance 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.<sup>[6]</sup></p>
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    <p>According to the statistics, the usage rate of targeted drug therapy has increased within ten years. In Figure 2, in 2003, targeted drug therapy is not commonly used compared with other therapies, accounting for only 11% usage. Over one decade, it is estimated that the usage of targeted drug therapy dramatically increases to 46%. It indicates targeted drugs therapy is a potential growing field and will become the commonly used therapy in cancer treatments in the near future.</p>
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Figure 2. The usage of targeted drugs.
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Figure 3. The usage of targeted drugs.
 
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<h2>Pre-diagnosis of targeted drugs treatment</h2>
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  <p>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<sup>[6]</sup>.</p>
  
 
   <h2>The concept of combination therapy</h2>
 
   <h2>The concept of combination therapy</h2>
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<p>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.<sup>[7]</sup> 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.<sup>[8]</sup></p>
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<p>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<sup>[7]</sup>. 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<sup>[8]</sup>.</p>
 
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Revision as of 20:06, 17 September 2015

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(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.

Properties and development of pre-diagnosis of 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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