Team:Nanjing NFLS/Integrated Human Practices

Integrated Human Practices

Integrated HP guides us to improve our project from three steps: necessity, feasibility, and impact. It mainly concerns P, H, O and C.

Apr.4^th |Interview with Zhigao Chen from Jiangsu Province Center for Disease Control and Prevention

We visited Jiangsu Provincial Center for Disease Control and Prevention and communicated with Zhigao Chen, the department director in CDC, to get the authoritative data on the incidence of cancer in China. To confirm the necessity of a new therapy against liver cancer, we visited Mr. Chen Zhigao, the department director of Jiangsu CDC.We learned that in 184 countries and regions around the world, the incidence and mortality of malignant tumors in China are above average. Some malignant tumors such as liver cancer account for about half of the world's mortality. According to Report on the Investigation of Malignant Tumors in Jiangsu Province, we found that the incidence of liver cancer in Jiangsu Province in recent years was 31.42/10⁵, accounting for 10.69% of the total incidence of cancer and ranking fourth in the incidence of malignant tumors. The mortality rate of liver cancer is 29.09/10⁵, ranking fourth in the incidence of malignant tumors.

The multiple statistics confirms the severity of this deadly disease and the drawbacks in existing treatments. All of us agreed that it is imperative to find new liver cancer treatment and therefore, we determined research direction

Here is interview report: CDCReport.pdf

Apr. 29^th – May. 5^th| Online survey

We conducted a survey to obtain public opinion on cancer therapy and synthetic biology. Specifically, we want to know their 1) awareness of cancer; 2) awareness of synthetic biology; 3) concerns about cancer therapies; 4) acceptance of synthetic biology and immunotherapy in cancer. We delivered the questionnaire through Wenjuanxing online platform, the largest online questionnaire website in China. We received 371 effective replies all over the country and even abroad. People are from different age ranges, education backgrounds, and careers. The sample size promised a convincing analysis.

Here's the questionnaire: Questionnaire.pdf

We discovered that

a). only 68.73% (255/371) know what cancer is. In samples of the elderly over 60, this figure is only 29.03% (9/31). Therefore, we believe that it is necessary to educate the public about cancer.

b). 53.64% of people are familiar with cancer treatment. People are most familiar with chemotherapy (95.84%), followed by surgery (87.94%) and radiotherapy (79.9%). Only half of the sample knows about immunotherapy (50.25%). But when we introduced people to immunotherapy, nearly half of them said they were willing to try (45.82%).

c). People have many dissatisfactions with existing cancer therapies: huge side effects (harm to normal cells) (87.06%), pain in therapy (83.56%), poor effect and high possibility of relapse (65.23%), and drug resistance (33.69%). However, immunotherapy is likely to solve these problems so our project selection is promising.

d). Considering that synthetic biology is a cutting-edge study that people are not familiar with, we briefly introduce synthetic biology in the questionnaire. To our surprise, most people accept its application in health field (83.83%). 93.53% of people are expecting its innovative application in cancer therapy, which dispels our concerns.

The results of the survey indicate that synthetic biology in cancer treatment can be accepted by the population and that immunotherapy can meet the demands of people in cancer therapy. We felt confident with our project and the public showed expectation for it. We also noticed that people are unfamiliar with cancer and synthetic biology. We designed activities about public engagement according to the status quo. (see public engagement for details) It is also worth mentioning that people are concerned about bioethics, which motivated us to include this element in our educational activities.

May.11^th| Interview with Prof. Shuying Ho from China Pharmaceutical University

We visited Prof. Shuying Ho for more advanced knowledge about immunotherapy in liver cancer. Prof. Ho told us that there have been new breakthroughs in the field of liver cancer treatment since 2017. For example, the immunotherapeutic drug PD-1 inhibitor is used in the treatment of liver cancer. Immunotherapy is a new facade in the field of liver cancer treatment. Although it is not a specialized effect drug for treating liver cancer, it has opened a new window for the treatment of liver cancer. Immunotherapy mode will guide future development of liver cancer treatment.

Prof. Ho's comment on treating liver cancer by stimulating the immune system through tumor neoantigen aroused our interest. We learned more about cancer immunotherapy, especially neoantigen. This coincides with our desire to transform cancer cells to treat cancer. Afterwards, we discovered that therapy based on neoantigen is limited by heterogeneity. Therefore, we discussed with PI and boldly determined to artificially construct neoantigen on cancer cells. Thus, the first version of C.I.T.H.A was born.

Here's the interview report: CPUReport.pdf

May.18^th|3^rdNanjing Regional meetup at China Pharmaceutical University

May 18th, we participated in the third Nanjing Regional meetup held at China Pharmaceutical University with 11 other teams from Jiangsu. We present the design of our project: Cancer Immunotherapy with Trojan Horse Antigen and exchanged ideas with judges and other iGEMers. CPU_CHINA provided us with constructive advice on tumor-specific promoters and “Trojan horse” antigen selection. They hinted at hTERT promoter, which they used last year. We also gave advice on project selection of SHSSIP-CHINA.

July.12^th|Interview with Dr. Ling Bofan and Dr. Wu Cunen from Jiangsu Hospital of Chinese Medicine

We interviewed Dr. Ling Bofan and Dr. Wu Cunen from Jiangsu Provincial Clinical Oncology Research Center of Integrated Chinese Medicine and Western Medicine for professional advice on immunotherapy. We selected several of the most common concerns about cancer treatment among cancer patients to communicate with two professionals for better understanding about this emerging cancer treatment technology. We learned that immunotherapy is a most-investigated cancer treatment method today with its huge advantages.

We present C.I.T.H.A Version 1 to them. Dr. Wu praised our idea of adopting artificial tumor antigens to stimulate immune system and expressed its effectiveness at the cellular level trial. However, from the perspective of the clinic, they are worried about the safety of the system and hope we can design double insurance to prevent its expression in normal tissue cells. Combining their suggestions with our PI’s, we chose to use ceRNA as double insurance. We added miRNA to HBsAg (“Trojan Horse”) expression system and new ceRNA activation system and CITHA 2.0 came to the world.

Here is interview report: JHCMReport.pdf

Aug.19th to Aug. 22th |6^th Conference of China iGEMer Community (CCiC) at Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences

We attended the 6th Conference of China iGEMer Community (CCiC), the largest iGEM team meetup at Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences. Experts in synthetic biology, former iGEMers and 70 iGEM teams from different universities and high schools gathered in Shenzhen from Aug.19th to Aug. 22th. We introduced our project in presentation and poster session and exchange ideas with other teams on cancer therapy.

Through extensive discussion, we received valuable suggestions from judges and other teams. iGEM Asia ambassador Nan Zhang gave us useful advice on integrated HP. The lecture sessions led by predecessors in iGEM were also of great help. We learned more about the current and future development of synthetic biology

Sept.13^th|Presentation at Jiangsu Province Center for Disease Control and Prevention

We visited Dr. Ge Yiyue and Dr. Zhu Liguo from Jiangsu CDC. Dr. Zhu Liguo specializes in liver cancer and presented our project. After being shown CITHA, they expressed their appreciation and support for our ideas and made suggestions for the future application of the project.

We do recognize that our project is today in the Proof of Concept phase, and tomorrow, it can be combined with immunological checkpoint inhibitors for the treatment of solid tumors. In the future, we can replace HTERT & HULC tumor-specific promoter and ‘Trojan Horse’ Antigen with other ones to solve different types of cancer.

Sept.30^th |Discussion with bioethics experts (Cong Yali, Cai Huiyuan, Hu Rui)

Since synthetic biology sometimes breaks the boundary between life and non-life, the development and application of synthetic biotechnology will also lead to unexpected ethical issues. How to maximize benefits, minimize risks should be our concern.

We emailed experts in this field, Prof. Cong Yali from Beijing Normal University，interviewed Cai Huiyuan from JSCDC, phone called Dr. Hu Rui from Hohai University and to discuss bioethical issues.

All three of them claim that, at the current stage, our project does not involve ethical concerns. However, Doctor Cai points out possible application of bioethics in the future stage of our project where we would consider how to transport CITHA to human body. For example, choosing Adeno-Associated Virus Vector instead of Lentivirus Vector to carry the plasmids will prevent the DNA sequence from being integrated into the host’s cells’ genome, thereby not triggering the controversy towards human gene editing.

Furthermore, the professors helped us form a fundamental understanding of the significance of bioethics in scientific research and the role of government, researchers and citizens. We also decided to promote bioethics values we learned to the younger generations and raise awareness towards ethical concerns in science that are sometimes neglected.

“People are the ultimate concern of ethics.” —— Prof. Cong Yali from Beijing Normal University

Here is the interview report summarizing the answers of the three: bioethics Report.pdf

Oct.15^th |Conversation with patients from Zhong-da Hospital

(To protect patients’ privacy, we used anonym)

We got in touch with Zhong-da Hospital, one of the best hospitals in Nanjing, and communicated with cancer patients monthly. They shared their stories of fighting against cancer and chatted with us to ease their nervousness.

On October 15th, Yongyi Wang interviewed Ms. H, a 78-year-old and a cervical cancer patient who received immunotherapy last year. Through a year's therapy, the physical condition of Ms. H has improved. Her experience helped us to recognize the significance of new treatments. Ms. H was diagnosed with cervical cancer five years ago. She has received different regimens of radiotherapy and chemotherapy, but cancer recurred after half a year, with symptoms of lower extremity edema, low back pain, and anemia. Moreover, she could not take surgery due to H's age. Therefore, H finally chose immunotherapy, obtained significant results and gradually stabilize the condition. Ms. H also described suffer and possible side effects that could be brought by chemotherapy She believes that our Trojan Horse strategy would be beneficial and reduce the suffering of cancer patients, which truly encouraged us.

The interview gave us a more intuitive understanding of the strong side effects of chemotherapy and the implication that there is an urgent need for new methods. At first, we were a little nervous about our project since it was based on a new theory but Ms. H’s words encouraged us. She strongly supported new cancer therapy research and assured that the general public would accept new bio-therapies. As technology develops, new therapies will show more of their advantages.

Here is the summary of conversation with patients: patientsReport.pdf