Overview
We are eager to understand the difficulties of stakeholders in a certain treatment area, and to contribute to it. Therefore, we conducted interviews with stakeholders to determined the direction of the project based on the combination of relevant literature, and we explored and improved the scheme step by step with the help of experts and professors.
We are people-oriented in the whole process. From the initial selection of project direction, the design of the project, to the final publicity, we stand in the perspective of stakeholders, and our core goal is to address the needs of the masses. Finally, we got positive feedback from the public return visit and expert comments, which indicates that we have made our contribution to tumor treatment while realizing the closed-loop between the demander and the target.
Select the challenge
Situation:
After team members’ brainstorming, we selected “oncotherapy” as our challenge field. However, there are so many problems to be solved in cancer treatment that we still don't know which one is the most concerned by stakeholders. Therefore, we need to go out of campus and conduct field interviews with stakeholders to obtain information.Our project stakeholders include doctors, patients, the general public, experts and professors. They can provide us with valuable opinions and suggestions from different perspectives, so as to guide us to determine the direction of the project and select specific implementation projects.
Implementation:
① We designed a questionnaire with six questions about the impact of cancer, the challenges of cancer treatment, and the public's understanding of and acceptance of new therapies.
② In addition to the questionnaire, in order to better understand the public demand, we also conducted interviews with a part of the public.
③ To further confirm how intractable relapse is, we interviewed another stakeholder group – physicians.
④ In order to get more authoritative advice, we interviewed Professor Guo Meng of the Immunology Department of our school.
⑤ We also reviewed the relevant literature on tumor occurrence and development.
Result:
The public questionnaire:
According to the results of the survey, we found that tumors were prevalent around the surveyed population, which indeed had a significant impact on people's lives.
Among the many problems in cancer treatment, the recurrence of cancer has attracted widespread attention, and 68% of the respondents think that the recurrence is one of the most difficult problems to solve in cancer treatment. So that got our attention, and maybe we could take cancer recurrence as our challenge.
At the same time, people's understanding and acceptance of new therapies also need to be improved, which suggests that it is necessary to popularize the relevant content.
The public interview:
The respondents’ answers were much the same. Relapse was mentioned in their responses, but their acceptance of the new treatment differed. Four of them were willing to follow up on our project, and we gave each other contact information so that we could return later.
The doctor interview:
We interviewed Dr. Wang of Xinhua Hospital and learned that the recurrence of tumor is indeed one of the clinical problems. What's more, the possibility of recurrence, to some extent, discourages treatment, delaying many patients who could be saved.
The professor interview:
We interviewed Professor Guo from the Immunology Department of our university. Professor Guo is an expert in CAR-immune cells. When he heard that we wanted to overcome the difficulties of tumor treatment, he suggested that we make a breakthrough in CAR-immune cells.
Literature query:
We reviewed the relevant literature on tumor occurrence and development, and found that tumor is indeed one of the medical challenges that should not be underestimated,1 and an important reason for the development and refractory of tumor is tumor heterogeneity, which is also a key factor causing tumor recurrence.2
Conclusion:
Through communication with stakeholders, we learned that tumor recurrence is a difficult problem for both the public and doctors, and tumor heterogeneity is one of the important reasons for tumor recurrence according to literature. Therefore, we finally decided to take tumor heterogeneity as the challenge of this project.
Reference:
1.Siegel R, Naishadham D, Jemal A. 2013. Cancer statistics, 2013. CA: a cancer journal for clinicians 63:11-30
2.Greaves M. 2015. Evolutionary determinants of cancer. Cancer discovery 5:806-20
Project promoting
Situation:
We have determined the direction of the project and the difficulties to overcome, but we have encountered some difficulties along the way, which were solved in the process of in-depth cooperation with ZJUintl-China
Implementation:
① Modeling optimization
ZJUintl-China discussed with us the oscillations of the initial simulation results of the prey and predator model, and suggested that we add a logistic term to take into account the relationship between the environment and the cell population to make the model more comprehensive. The simulation results of the improved model are consistent with the real situation.
② Circuit optimization
During the online communication with the team of International Union Department of ZJUintl-China, we fully understood each other's project content and promotion process, and put forward valuable suggestions. In the initial construction of the plasmid, they found that we were using three plasmids, which would make transduction inefficient, and suggested that we find a way to combine the two plasmids to improve the efficiency. We took their suggestion and constructed a new plasmid by reviewing the literature.
Project evaluation and optimization
Situation:
Through literature review, team discussion, and faculty guidance, we designed CAR-NK92 cells and its suicide route, and verified the success of its expression, lethality and specificity by cell experiments. But we weren't sure if our experiment would be approved by the professionals and how it would be improved to be able to solve the problem of tumor heterogeneity.
Implementation:
In order to further improve the project, we reported our current project progress to Professor Guo from the Department of Immunology and Research of our university and asked him to give comments on our experiment.
Result:
Professor Guo affirmed our current progress and pointed out that the current ten Cars are prespecified in advance, and we need to further complement and improve them to deal with the unknown neoantigens.
Conclusion:
According to Professor Guo's instructions, we identified the next hurdle——how to use our CAR-NK92 cells to deal with unknown neoantigens.Neoantigen is one of the key factors of tumor recurrence, which is also the key difficulty to be overcome in this project. It is the product of tumor heterogeneity and has the characteristic of randomness. How to defeat neoantigens with existing materials and technologies and overcome tumor heterogeneity is a problem we are facing now.
Complete the loop
Situation:
We have already answered one part of the needs that we have previously heard from our stakeholders --addressing recurrence. Now, with the core part of the project completed, we need to address the needs of the other part –publicity and education related to the project, synthetic biology and synthetic immunology.We know from previous investigations that the public knows little about synthetic biology, even the meaning and use of synthetic biology. As an emerging class of science, synthetic biology plays an important role in production and living. It is necessary for us to make some efforts to improve its popularity, so that the audience can understand its basic principles, master basic knowledge, and apply it to solve some problems. For this purpose, we have taken a series of measures to achieve our goal. In order to demonstrate that our program can actually bring benefits to patients, we also conducted a cost analysis and presented it on the Wiki. In addition, we also helped ZJUintl-China complete the cost analysis.
Result：
① Education
WeChat offical accounts
In the mass interview, the interviewees clearly expressed their hope that our science popularization could be as understandable as possible. Therefore, we not only used vivid illustrations, but also personified cells, and told our project in the form of stories in easy-to-understand language to promote and popularize our project on wechat offical accounts. At the same time, we also use the wechat public account platform to promote and educate synthetic immunology, from the concept of synthetic immunology, current situation to future prospects. In addition, we also reprint the related knowledge articles of synthetic biology for fans to read.
Educational Resource Package
We made educational resource packs for middle school students, including introduction to our project, introduction to synthetic biology and synthetic immunology, introduction to iGEM competition, etc., so as to stimulate the scientific research interest of middle school students and cultivate their thinking of synthetic biology while promoting education.
Campus presentation
For college students, we held a lecture on synthetic immunology to educate the synthetic immunology and arouse the students' interest in scientific research, as well as publicize the iGEM competition.
② Cost analysis
We summarized the results in the table.
We also helped ZJUintl-China to completed their cost analysis.
Prove the closed-loop
Situation:
We have completed the project to the best of our ability, but we do not yet know whether our research will be helpful to the cancer treatment field and society, so we need to conduct further interviews with stakeholders
Implementation:
We first invited Prof ZHOU Jingying from the Chinese University of Hong Kong to give a general evaluation of our project.
In addition, in order to return to the original intention of our project, we also need to make a return visit to the previous interviewees to test the effectiveness and benefit of our project content and popularization of science
Result:
We conducted the popularization of our own project, synthetic biology and synthetic immunology through numerous online and offline platforms including the official Wechat account, using vivid and interesting language to make it easy to accept. We returned the interview to four interviewees, all of whom fully affirmed our project and said that they were looking forward to the implementation of the idea.Besides, through the number of page views and the number of likes, we can preliminarily judge that our promotion has a certain effect.
The professor gave full affirmation to our project, and believed that our project was complete and convincing, especially in the cell experiment and mathematical modeling, which showed the feasibility of our project. In addition, the professor added the advantages of our project: compared with the short half-life of CAR-T, we can effectively control the lifespan of NK cells by using suicide circuit to control apoptosis, so as to better exert the killing effect. In addition, the professor also raised her concerns about the safety of our project, thinking that even with the guarantee of suicide circuit, injection of NK-92 still has certain safety risks. We have given full consideration to this and reflected this in the safety section.