Foreword
From the beginning we strived to create a project with the highest implication for society and the research environment around us. We believe that integrating the concerns and feedback from all the stakeholders affected by the project is really important to ensure that the new developed technology can be easily adopted and complies with current regulations and practices. This is especially important with a disease such as cancer. By integrating human practices into our project we have been able to create a project that transcends the laboratory bench and aims to have real world implications in the future of cancer treatment, by meeting the current unmet medical needs. Our main collaborators in the project range from university researchers to oncology clinical experts and other therapeutics specialists.
From our multiple consultations with them we were first able to understand the process that patients and clinicians have to go through to remove the tumor and cure the cancer, which gave us important insights into the limitations and problems of current cancer treatments; secondly, we were able to exploit the strengths that our technology has in comparison with the current state-of-the-art cancer treatments; and finally, we got to see how research is being slowly translated from a research project to fully tested systems in the hospital.
Recent years have seen a new wave of innovative and effective new therapeutic approaches attempting to cure cancer in its different modalities, the complex mechanisms of its genesis and even the different methods of combating, are not completely defined and understood. This problem stems from the complexity of the disease itself, and huge efforts still have to be made in order to fully understand the disease.
We believe that currently one of the most promising weapons against cancer is immunotherapy! And we are not alone, research groups from all over the world believe that there is great potential for the the future of immunotherapy.
Immunotherapy however, like any other technology that is in the vanguard and at the edge of innovation, has a limited clinicals implementation and the majority of the systems still require extensive validation. We believe that synthetic biology and novel innovative approaches could really further advance immunotherapy development.
With this in mind we set up the main ambitions for our technology:
First, we wanted to create a holistic pipeline that integrates different parts of the treatment, from personalized vaccine design to follow-up;
Secondly, we wanted to increase the accessibility and production efficiency of neoantigen-based cancer vaccines to target cancer by creating a highly personalisable, fast and cost-effective system; Finally, we are hoping to provide a cost-effective approach accessible to lower income communities and smaller hospitals, ultimately reducing the cost for patients and healthcare systems.
ORIGINS
The origins of CAPOEIRA began far from what it is today. During the ideation process of choosing a project, we took our time in discussing different possibilities of a project and decided to remain open throughout the process, exploring every possibility. Our ideas ranged from using synthetic biology to detect the quality of wine, to early diagnosis of tuberculosis. We researched thoroughly through the decision making process and spoke with specialists in the respective fields within EPFL to explore the feasibility of each idea.
At the time, we explore ideas about cancer diagnosis as well as personalized cancer immunotherapy and during our research into the topic and consulting experts in the field, there was a spark of an idea to merge the two ideas with synergie into one coherent project. We’ve been very lucky to meet the Prof. Elisa Oricchio who is leading the research on the genetics of lymphoma and its translation into new therapies in the Oricchio Laboratory here at EPFL. We received her advice at a very crucial stage of our project; the idea development. From an initial talk the team had with Professor Elisa Oricchio, we learned about using ctDNA as a potential biomarker for cancer.
CAPOEIRA : Integration
During our meeting she has given us a lot of precious advice, one of which had a considerable impact on our work: using circulating tumor DNA (ctDNA) as a way of detecting early stage cancer. Subsequent to this meeting we agreed on integrating her inestimable advice in what today is our follow up part: detection of cancer relapse through ctDNA. For that reason we are immensely grateful.
At the same time, when the team sat down for the first time to discuss the project idea, we had in mind to focus on a problematic that had global repercussions. Being an iGEM project wanted to highlight the capacity of synthetic biology to affect real world problems, and furthermore create a project that could potentially treat cancer in a realistic scenario. Even though this process was challenging, we found that the project revolved around a great number of stakeholders and would have a great impact on society, would also create a good environment for collaboration and combined research efforts as you will discover through our Integrated Human Practices story of CAPOEIRA.
First Steps: Understanding the Problematic
When faced with a problem as challenging as curing cancer, it is really important to understand the whole picture. In order to do so it was important to define all stakeholders considered in the project and evaluate the risk and problems associated with each of them. One of the most evident stakeholders are the medical experts and clinicians treating patients. Although sometimes clinical practices differs far from what is being done in the research laboratories in terms of innovation, medical professionals are one of the key connections that researchers can have with patients, and furthermore, they understand the needs and struggles of cancer patients.
So we started our search for a collaborator that could help us in this situation, and the first place to go in Lausanne if you need a medical professional is the CHUV ( Lausanne University Hospital). We were fortunate enough to have a meeting with MD, Prof Olivier Michielin, Chief of the Analytic Personalised Oncology Division at CHUV Hospital in Lausanne. Doctor Michielin has focused on translational oncology, developing new molecularly defined therapeutic approaches based on original in-silico techniques developed in his laboratory. His specific field of treatment is coincidentally melanoma, so his daily tasks consists of inspecting and supervising the treatment that the melanoma patients will receive at CHUV Hospital.
Today’s Practice: Melanoma
Doctor Michielin explained that the current typical process for treating a patient with melanoma begins when the melanoma is detected and confirmed after pathological examination of a surgical extraction. Then, depending on the severity of the cancer and the risk relapse, the patient is monitored with CT scans to detect any signs of metastasis. It is also at this part where the oncologist can propose a immunotherapy, specially in patients where there is still some microscopic residual disease. Nowadays, Doctor Michielin’s unit uses immunotherapy in indicated situations. Once the treatment is ongoing, the patient is followed and if further signs of relapse appear or the cancer becomes metastatic, then the oncologist will revisit the immunotherapy or even use combined therapies, for example combining two checkpoint inhibitors (Ipilimumab, Nivolumab). However, these therapies are fairly toxic, while still showing a good response rate in patients compared to previous therapeutic modalities. By this time, some of the patient’s will positively respond to the therapeutics, however, he insisted that monitoring of the therapeutic effect at this stage is key.
Doctor Michielin explained that currently one important aspect in assessing the correct therapy is first to understand the mechanism of resistance of the specific cancer. Furthermore, he pointed out that it is key to understand how the disease adapts to the proposed treatment to avoid patient exposure to high levels of toxicity, which can be extremely inconvenient for the patient and cause important side effects. This made us realise the importance of finding a method for detecting the vaccine therapeutic efficacy. By reducing the time between when the treatment is implemented and the patient shows signs of toxicity, we could quickly adapt the treatment if we see signs fast enough.
One important suggestion Prof. Michielin made was on the neoantigens monitoring. Our initial idea was to use the neoantigens identified in the bioinformatic part of our project to detect a potential relapse. He explained to us that it would be more suitable for monitoring the personalised vaccine efficiency, as their initially increasing levels could indicate tumor lysis and ctDNA release in the blood. Also, he made us aware that relapse might emanate from another population of tumor cells not initially targeted by our vaccine and thus might not be detected by using the same neoantigens. This led us to consider alternative biomarkers, ctDNA with different mutations or chromosomal rearrangements, or miRNA.
CAPOEIRA
Overall Doctor Michelin considered CAPOEIRA as a ‘very interesting and ambitious project’. However, he pointed out that it would require a huge amount of work to produce and validate effectively all parts of the project. We took these comments with great optimism and decided to focus mainly on the parts that he found that more significantly fill the gap in today’s medical practice. He specifically outlined some potential impacts of CAPOEIRA:
One point of our pipeline that he considered very interesting is the transferability to GMP (Good Manufacturing Practices) process, that currently is one of the biggest limitations of antigen-based vaccines. Nowadays, to reach GMP level of production of one single peptide for a single patient the is in the 150’000 CHF or USD ballpark. GMP is a necessary requirement for any therapeutic to be used for clinical trials. The idea of having a system that follows GMP, to produce a large number of peptides automatically could be an important breakthrough in the field.
CAPOEIRA : Integration
Furthermore, Doctor Michelin pointed out that since we are basing CAPOEIRA vaccine expression in a cell-free expression system there would have several advantages.
Furthermore, recent developments in the biotechnology field indicate the possibility of reaching GMP levels with cell-free expression systems. For example, Sutro Biopharma a company based in San Francisco, has just confirmed the first GMP certified cell-free system to produce antibody-drug conjugates.
The accessibility and the ease of use of the tools that we are developing. Doctor Michelin, outlined that even within Europe, there might be hospitals or clinics that have limited access to the most up-to-date tools for analytics and patient follow-up.
Although Doctor Michielin currently works as the Head of the Personalized Analytic Oncology Division (with a Specialized Consultation for Melanoma) at CHUV, he is also an Associate Professor and Group Leader at the University of Lausanne for Computational Oncology and Molecular Modeling. We are extremely grateful and privileged to have received his input throughout the project because one distinguished quality that is highly appreciated is the knowledge, experience and involvement he has in the treatment of melanoma cancer.
His range of experience and expertise that encompass not only the clinical aspects of treatment, but also the more technical concepts, helped us a lot in CAPOEIRA since we received important input concerning the specifics of our therapeutic approach, as well as the things to look into more detail when envisioning the use of these treatments to patients in medical facilities.
Exploration of the Therapeutic Approach
One of the main topics of discussion we had with Doctor Michelin, was the selection of a correct neoantigen. Research has shown that the MHC Class I complex will often only present 9-10 amino acid long sequences. However, Doctor Michelin suggested that sometimes embedding the neoantigen sequence into a bigger peptide or protein of around 20 amino acids long could have a positive impact in the signal response of the vaccine. The main difference relies in that the longer peptide sequences can not be presented in the cell surface without the processing of the proteasome. This machinery plays a vital role in the activation of the dendritic cells and hence the overall immune response of the therapeutics. As our peptide is attached to a protein, such processing will indeed be required. Moreover, we believe that it is possible to have a longer peptide attached to the encapsulin protein without modifying our process.
CAPOEIRA : Integration
For this reason, we plan to address this feedback by exploring the use longer sequences in the future. This can be done by the neoantigen and a short part of the sequence exploit if this approach has better effectivity in the dendritic cell assays. Furthermore, we have ensured that our system allows expression of peptide sequences longer than 25 amino acids allowing longer peptide sequences to be added.
One common question that arises from discussion was on the number of neoantigens used in the personalized vaccine, with the potential concern of having too many targets for the immune system to handle. He did not have any research evidence or data to suggest, but he was hopeful that the immune system is capable to do things in parallel and target multiple neoantigens at a time. Furthermore, he pointed out that targeting multiple neoantigens may even help to reduce the occurrence of relapse, due to the redundancy of the vaccine that limits the options for the cancer to escape and metastasize.
CAPOEIRA : Integration
We therefore used it as our strategy to fight melanoma. Doctor Michielin found that it would be a decisive approach of CAPOEIRA’s. The use of high-throughput therapeutics by using combined neoantigen delivery to target multiple cancer clone populations.
Finally, he added that antigen-based therapeutics have the possibility of being combined with checkpoint inhibitors further improving the effectivity of the latter therapies. Indeed, checkpoint inhibitors might enhance personalized vaccines by removing the brake on T-cells posed by immune checkpoints, and conversely, personalized vaccine, one could imagine that the personalized vaccine would provide the necessary targets to an immune system boosted by checkpoint inhibitors.
The Prospect of Follow-Up
Doctor Michielin considers it very interesting to focus the detection system not only in the specific point mutations extracted but also focus on the chromosomal rearrangements. As explained in the follow-up section of CAPOEIRA, ctDNA containing specific chromosomal sequences are a promising target for detecting relapse months before current detection techniques. Furthermore, he considered that it also will be a good approach to create a wholistic project and combine the approaches by production of a neoantigen personalized vaccine accompanied by a monitoring of the vaccine efficiency by targeting the specific mutations coding for neoantigens in the patient ctDNA using the same detection scheme as in the follow-up part of the project (target specific amplification and Cas12 detection). This could help clinicians to quickly iterate the vaccine formulation and redesign the therapeutic approach for each patient.
CAPOEIRA : Integration
At this point in CAPOEIRA, we were currently testing our Cas12a detection system for the detection of chromosomal rearrangements in ctDNA, however after the importance of this medical need, we quickly also turned our attention into adapting our system to detect point mutations so that we could detect the neoantigen-vaccine efficiency.
Finally, he recommended that although we might be interested on contacting various patient associations to discuss the project, the current status of the CAPOEIRA and the overall vision is more aimed towards clinicians and researchers. In order to bring in patients, you often need to have a scientific proof of concept, and then you can ask these questions down the road.
Personalised Medicine: the new trend!
Personalized medicine is a big trend. You don’t need to dive deep to see that this approach is changing the healthcare and medical practice around the world.
As the Vice President of Healthcare and Life Sciences at Frost & Sullivan, Reenita Das, points out, personalised medicine is the end of the ‘one size fits all’ healthcare model (Forbes Inc.. 2017). One of the drivers of this transition is the global trend to reduce overall healthcare costs combined with the improvement of target therapies. Another factor that is drastically pushing this new paradigm is the drop of cost and time necessary for genomic analysis, which makes personalised therapy based on genomic diagnostics an appealing strategy.
Another factor that is drastically pushing this new paradigm is the drop of cost and time necessary for genomic analysis, which makes personalised therapy based on genomic diagnostics an appealing strategy.
CAPOEIRA : Integration
To understand how we can take advantage of all the benefits of personalised medicine in the core of CAPOEIRA we reached out to different stakeholders. We also aimed to understand how this swift in the healthcare paradigm will affect the future years of melanoma treatment and in oncology.
According to Doctor Olivier Michielin, at CHUV they have already reach a high level of personalised medicine. Under his group currently, before treating a patient they need to know the status of five driver oncogenes, including BRAF mutations and NRAS, as well as PDL1 status. Current limitations are the know-how: how to deal with all patient data and output a single therapy.
Doctor Michielin’s group often performs multiple assays on the extracted samples, including, immunohistology, slides, non-stained tissue measurements and live tissue analysis by treating the tissue with different drugs. He pointed out that sequencing is what currently they perform the most. This is not only due to the decrease of cost and time of the sequencing technologies but also the hospitals are encourage by the insurance company policies, which now provide full reimbursement of full coverage genome analysis for hospitals.
We were also curious in understanding if there are any other methods to extract patient data in order to design an antigen-based vaccine however Doctor Michielin said that at the moment sequencing is the obvious way of extracting the specific sequences and cancer neoantigens.
CAPOEIRA : Integration
Given the increasing accessibility of sequencing technology, we were encouraged to continue developing our bioinformatic pipeline that would be based on the whole exome sequence of patient’s cancer cells, and that it would not be a bottleneck in the future for the accessibility of this technology.
At the same time, we wanted to understand how this shift towards personalised medicine is affecting the pharmaceutical and biotech industry. In 2017 the top three big pharma companies in cancer research (Roche, Celgene and Novartis) accounted for almost 50% of the global market share of cancer treatments (Statista Inc., 2017). In order to get this link to the industrial side we contacted Prof Roger Clerc, who is currently a guest professor at EPFL.
He has a strong background in translational research and drug discovery in the field of metabolic diseases by directing a preclinical group at Roche Ltd, which specifically worked on atherosclerosis and Type 2 diabetes. Roche is the leader worldwide of cancer therapies and treatments and seeing how such a large company is transitioning towards a regime of personalised medicine can have an impact in the evolution of the industry.
When speaking to Prof Roger Clerc about the project and the prospects of the project for the future, he really stressed that the project should address a specific medical need and we should think about it at each stage of the project. With his experience in the pharmaceutical industry, we talked about one of the steps needed in advancing the project is testing in a rodent model. We also discussed about the different steps that would be necessary in addition to this as well as from a regulatory perspective. He is very optimistic about the project with the opinion that “diagnostic biomarkers are the future, not only they reduce the cost of hospitalisation but also reduce the disease burden for patients”.
The Evolution of CAPOEIRA
As we went along the project, reading papers, discussing with researchers in our scientific environment, trying different ideas and setups for experiments, CAPOEIRA evolved. And in order to evolve CAPOEIRA in a mature way, we tried to interact with the cancer research community around us by attending seminars and conferences that go beyond our project.
Lausanne is one of the very few locations where cancer research is supported by the Ludwig Institute. In the scope of our project we have integrated a close interaction with clinicians and they have guided us on how to proceed with our project.
We are extremely lucky to be situated in Lausanne, given that it is an extremely unique place for cancer personalised research surrounded by world renowned institutions. will focus on broad themes – horizons – in cancer biology and therapy. This symposium will also present the new multi–institutional Swiss Cancer Center (SCC) which leverages complementary expertise from our partner institutions: the University Hospital & Medical Center (CHUV) of the University of Lausanne (UNIL) , the Swiss Federal Institute of Technology Lausanne (EPFL), Ludwig Cancer Research (Ludwig), the University Hospital & Medical Center (HUG) of the University of Geneva (UNIGE), the Swiss Institute for Bioinformatics (SIB) and the ISREC Foundation. This unique environment has been extremely helpful in order to mature the concept of CAPOEIRA.
One of the actor’s that has taken part in our project is Prof. Daniel Speiser, who is a Professor in clinical tumor biology & immunotherapy at UNIL. During our conversations his knowledge on the translation of therapeutics to the real world and the mechanisms of immunology have been invaluable to address future concerns in our therapeutic approach. One of the remarks that was repeated was the limitations and side effects that delivering an elevated amount of neoantigens could have in the patient and in the overall efficacy of the vaccine. Although, he was not able to specify a fixed number of neoantigens as the optimal therapeutic target, he pointed out that although neoantigens that are not immunogenic might not be harmful for the patient, it might dilute the overall signal of the targeted neoantigens. The problem is to find a balance between presenting a great number of neoantigens, to ensure there are some immunogenic neoantigens present in the therapy and potentially diluting the elicited immune response, or delivering a narrower library of neoantigens to ensure that the ones that have a real immunogenic response are presented by the DCs, with the risk of missing out on potentially immunogenic ones. Prof. Daniel Speiser, suggested that one attempt to reduce this problem is instead of attaching different neoantigen types to one single assembled encapsulin, to assemble the same neoantigen to each monomer, creating a encapsulin nano protein containing a single neoantigen allele. This confronted us in our plan which was indeed to have unique neoantigen-encapsulin constructs, which can be later combined as a library for the personalized vaccine formulation. This will reinforce the immune response of the neoantigens that have potential for presentation on dendritic cells, in favour of the ones that have no immunogenic effect. Prof. Speiser also remarked to what Doctor Michelin mentioned before, consider the presentation of longer peptide sequences containing the neoantigen in our vaccine, instead of delivering just the neoantigen sequences alone. Finally, for the cancer follow-up part of the project, Prof. Daniel Speiser, suggested not to focus only on the detection of mutated ctDNA, but also to consider detecting non-mutated sequences that are differently regulated in patients with cancer.
CAPOEIRA : Integration
Given Prof. Daniel Speiser’s input on the project, we believe that all his considerations should be taken into account in the future development of CAPOEIRA. Unfortunately, until this point of the project, we have been limited to the use of the OT-1 peptide, to validate the presentation efficiency of the cells. However, having libraries of encapsulin containing a unique type of neoantigen will be explored and we have already envisioned the possibility of testing the efficiency of encapsulin-neoantigen personalized libraries after the project with in-vivo experiments on mice, potentially with the collaboration of the Laboratory of Biomaterials for Immunoengineering at EPFL.
ISREC Conference
The team was able to attend the Horizons of Cancer Biology and Therapy 2018 Conference on cancer biology and therapy organised by the Swiss Institute for Experimental Cancer Research (ISREC) hosted in Swiss Conference Centre. This symposium also presented the new multi–institutional Swiss Cancer Center (SCC) in Lausanne which leverages complementary expertise from our partner institutions: the University Hospital & Medical Center (CHUV) of the University of Lausanne (UNIL) , the Swiss Federal Institute of Technology Lausanne (EPFL), Ludwig Cancer Research (Ludwig), the University Hospital & Medical Center (HUG) of the University of Geneva (UNIGE), the Swiss Institute for Bioinformatics (SIB) and the ISREC Foundation. During the conference we got the opportunity to present our project through our poster and meet leading clinicians and researchers from all over the world that are also trying to find new cures to cancer. Furthermore, through numerous research presentations from experts around the world we were able to see what kind of treatments and ideas they are currently testing to target and treat cancer today.
Frontiers 2018
We also had the privilege of attending 'Frontiers2018' -- Symposium on Frontiers in NanoBio Engineering and Medicine - EPFL organized jointly by EPFL, the University of Tokyo and the Tokyo Medical and Dental University. We were able to learn the different approaches used in Engineering and Medicine for solving a diverse range of problems, not just related to cancer. In addition, we got to present our project through our poster at the conference to professors and researchers. It was a great opportunity to learn from, the lectures and the feedback we got were inspiringly insightful, especially because the feedback came from researchers with diverse backgrounds.
CAPOEIRA : Integration
During the symposium we got to meet Prof Suliana Manley whose research focuses on the use super-resolution fluorescence imaging techniques combined with live cell imaging and single molecule tracking to determine how the dynamics of protein assembly are coordinated. We were able to receive feedback regarding the dynamics and energies of our experiments and ways that we could improve and optimize them to obtain better results.
We also got the chance to discuss our bioinformatic pipeline for neoantigen discovery and ctDNA mutation detection, by talking with David Gfeller, Head of Computational Cancer Biology Group at Swiss Institute of Bioinformatics and member of the Ludwig Institute for Cancer Research Lausanne. His field of research focuses on the development of computational biology and immunoinformatics tools to better understand the interactions between immune and cancer cells. Within our Ginga pipeline, he is more on the prediction of the binding affinity of MHC-I complexes and antigens. However, compared to current tools like netMHC, his group use mass-spectrometry data from the HLA molecules to guide the predictions of the software. David Gfeller, also gave us an overview of the current state of the field of neoantigen discovery and the use of bioinformatic tools for improving immunotherapy targeting. He remarked that currently discovering neoantigens is one of the greatest limitations for developing a personalized vaccine, and that currently only 5% of the candidate neoantigens, that are selected by the bioinformatic tools have a real immunogenic response directed against cancer.
CAPOEIRA : Integration
After discussing the possibility of a collaboration, we decided to implement his HLA-peptide binding software in our pipeline to find the best neoantigen candidates. We believe that this implementation will improve the precision of Ginga, however currently we are unable to validate this claim.
Furthermore, we would like to point out the figure of George Coukos, Director of the Department of Oncology at the University Hospital of Lausanne which is one of the main advocates in Lausanne for bringing personalised medicine to the area of cancer therapy. Together with Prof. Lana Kandalaft, they were able to recently present a personalized dendritic cell vaccine for ovarian cancer by pulsing dendritic cells with oxidised tumor lysate. Even though we were not able to meet during our project, we meet with some of the researchers from his laboratory during the ISREC conference to discuss the project. For more information about George Coukos view about personalised medicine and the current state of personalised oncology in Switzerland, please check the links below.
https://www.chuv.ch/fileadmin/sites/onc/documents/onc-the_doctor__gr__interview_george_coukos.pdf
https://www.chuv.ch/fileadmin/sites/onc/documents/onc-cancer_world_gc_profile_jan-15.pdf
Interacting with the SynBio Community
We also were determined to get in touch with the synthetic biology initiatives around us, to understand how the use of synthetic biology has grown beyond the traditional sense, given how quickly the field has grown in recent years.
We got to meet with Luc Henry from The Hackuarium association, a biohacking space with the aim "to bring biology (and biologists) to the world, and the real world back to biology in a neutral, open, noncompetitive and not-for profit environment." We spoke with him in order to understand how to engage the public about synthetic biology in interactive and innovative ways.
CAPOEIRA : Integration
Prior to our meeting we envisioned an event that had goals to sensibilize and create awareness of SynBio through diverse platforms, bring different stakeholders together, highlight ethical questions and finally discuss the democratization of engineered biological systems. In order to do so, we spoke to Luc Henry for advice about how to proceed with the event and for potential contacts of people working on projects that use synthetic biology in interesting ways. The event was centered around the ethics, economics, safety and policy of synthetic biology as well as the relationship between art, engineering and biology. We unfortunately were not able to organise it before the Jamboree however we met some very inspiring people in the biology community.
Here is the Event Proposal that we prepared:
Event Proposal
During our research into the ethical aspects of CAPOEIRA, we realised that Art could be a tool to bridge the general public and scientific research, with a focus on biology. This was a great opportunity to raise awareness of synthetic biology and biology to an audience in a way that is appealing and less intimidating.
We got in touch with Veneta Valeria Gerganova, responsible of the “Figure 1.A” exposition in Lausanne, Switzerland. The aim of the exhibition is to celebrate the beauty of science and all the hard work behind it through images submitted by the members of the Faculty of Biology and Medicine at University of Lausanne. A selection of photos selected by a multidisciplinary jury and then portrayed in the “La Sonnette” Gallery, in the City Center of Lausanne, was open to the general public.
CAPOEIRA : Integration
Inspired, we created a photo contest among iGEM 2018 teams, and photos that we received during the competition are exposed on our wiki in our Collaborations Page. This meeting also highlighted the importance of visuals for our project presentation, shared images, graphics, colors, layout of ideas, legends, etc. It led us to comprehend the importance of visuals at first sight during a presentation, poster session, and we hence payed more attention to these attributes in the designs that we created later on for CAPOEIRA. Although our conversations with the synthetic biology community did not revolve directly around cancer, it was important for us to understand the landscape of communicating synthetic biology with the public, and to be aware of the entry diverse entry points that the general public has to a topic such as synthetic biology that is still controversial today.
CAPOEIRA: The Next Steps
As CAPOEIRA evolved and matured we developed interest in taking next steps. We have shown that our system can work and be validated, but what is required to take it from where it is now all the way to the clinic?
For CAPOEIRA, we wanted to understand how relationship between all the stakeholders would come into play as the project would enter the cancer therapeutic market. In that spirit, we attended a roundtable discussion at the event called Planète Santé (‘Healthy Planet’ in English) concerning our project in order to develop an overview of the needs of cancer treatment from the different stakeholders titled “Cancer : The Indispensable Partnership Between Fundamental Research and Patients”. The panel consisted of Prof. Dr. Olivier Michielin (Chief of the Analytic Personalised Oncology Division at the Lausanne University of Hospital CHUV), Prof Pierre-Yves Dietrich (Head Doctor of Service, Head of the Oncology Center of the University Hospitals of Geneva), Dr Michael Sagara (Associated Doctor and in charge of Specialized Psychiatric Consultations at CHUV), Prof Georges Cuokos (Head of the Oncology Department UNIL-CHUV), Prof Christine Bouchardy ( Director of Geneva Registry of Tumours), Michèle Constantin (Vice-President of the Patient Information Association) and Prof. Manuela Eicher ( Associate Professor at the University Institute of Formation and Health Research).
This panel contained a rich diversity of representatives from all the stakeholders surrounding cancer treatment and we have described the insights we gathered in our Public Engagement Page.
As we are targeting the therapeutic industry (specifically cancer therapeutics) and since entering this industry needs an intellectual property (IP) along with necessary approvals, it was not feasible for us to search for investors in this stage of our project. Rather, we focused on early stage funding programs that could help us fill the gap between our current stage (a proof-of-concept) and fundraising stage.
CAPOEIRA : Integration
In our meeting with Marco , we discussed what we have done in our project and tried to align our offering to what the market needs are. We then discussed about funding strategies and how we can proceed with filing a patent for our technology. We then agreed to continue our mentorship relationship after iGEM competition.
For further developing our technology, we are also in the process of applying for Catalyze4Life program. Catalyze4Life is the School of Life Sciences program, which tries to fill the fundraising gap that exists in applicable technologies in the health-care industry.
CAPOEIRA : Integration
For doing so, we contacted Kostas Kaloulis, manager at Catalyze4Life, to start the process of writing the proposal for getting the support, which enables us to receive initial funding, lab space, and necessary mentorship during our technology development and preclinical phase. The result of our application will be available after 29th of October, 2018.
Throughout our discussion with those people, we found out that the most critical aspect of commercializing our technology and getting funds, is to have an intellectual property. For this reason, we also contacted the Technology Transfer Office (TTO) of EPFL to further investigate the potential of our technology for filing a patent.
CAPOEIRA : Integration
We had a meeting with Mauro Lattuada, Technology Transfer Manager at EPFL, to further discuss the process of filing a patent for the case of our technology. We decided to keep some parts of our technology confidential and avoid revealing them during the Giant Jamboree, to be able to file a patent afterwards. Furthermore, we are in the process of applying for the IMAGINE IF! acceleration program, where we can receive tailored mentoring and access to a professional network while competing for non-dilutive funding that will allow us to take our venture to the next level. The application round of this program has just started and we will participate in the IMAGINE IF! Event, which will happen on October 23rd, 2018.
Now, we are eagerly awaiting the iGEM competition to start our adventure towards our new venture! In addition to the information here, we performed an analysis preparing CAPOEIRA for the next steps in our Entrepreneurship. It would be a great opportunity to understand how other teams have ventured into start-up businesses as well as we would receive a great amount of feedback of our projet, as it is far from over for CAPOERIA!
References
Forbes Inc.. 2017. Drug Industry Bets Big On Precision Medicine: Five Trends Shaping Care Delivery. [ONLINE] Available at: https://www.forbes.com/sites/reenitadas/2017/03/08/drug-development-industry-bets-big-on-precision-medicine-5-top-trends-shaping-future-care-delivery/#5c4c37535d3a. [Accessed 15 October 2018].
Statista Inc.. 2017. Top 10 pharmaceutical companies based on global oncology market share in 2017 and 2024. [ONLINE] Available at: https://www.statista.com/statistics/309711/oncology-market-share-of-top-ten-pharmaceutical-companies-worldwide/. [Accessed 15 October 2018].