Overview

Incidence

As we all know, China is the largest low-income or middle-income country and the most populous country in the world. And the breast cancer is the most common cancer in Chinese women，just as the whole world. By looking up to the data and papers, we know that the incidence of breast cancer in china has increased more than twice since 1990s, which rise as same as global rate. Form the newest data about the status of tumor in china, the incidence of breast cancer is 17.10% in 2015, which is higher in the city and about 27.4% in ShangHai.

Mortality from the breast cancer rose during the past 30 years in china, and in urban areas mortality increased by 100%, however in rural areas mortality did not increased a lot ( the data is shown in the picture2, which is cited from the paper: Breast cancer in china).

Through huge numbers of study about breast cancer, we know some risk factors for breast cancer in Chinese women.

(1) Reproductive and hormonal factors——eg, a long menstrual life, nulliparity, increased age at first livebirth, limited breastfeeding, and the low fertility rate;

(2) Obesity in premenopausal and postmenopausal women and low levels of physical activity——eg, Chinese women (both premenopausal and postmenopausal) with a body-mass index of 24 kg/m² or higher had a four-times increased risk of breast cancer compared with women with a body-mass index of less than 24 kg/m²(cited: A case-control study on risk factors of breast cancer in China)

(3) Family history;

Current strategies

Nowadays, in China, there is a systemic diagnosis and treatment process, which is shown below (Picture 3) It confirm the diagnosis by the specific and typical breast cancer signs and other auxiliary inspections like tumor maker, imaging detection tissue biopsy and so on.

The treatment of breast cancer includes surgery, radiotherapy, chemotherapy, endocrine therapy, molecular targeted therapy and so on. According to the pre-treatment assessment, doctors performs systemic and topical treatment. There are some common treatments which is listed below.

(1) Surgical treatment: modified radical mastectomy, simple mammectomy, breast preservation breast surgery;

(2) adiation therapy;

(3) Chemotherapy;

(4) Endocrine therapy;

(5) Molecular targeted therapy;

(6) Comprehensive therapy;

After the surgery or the first step of therapy, doctors normally monitor the tumor size and metastasis by detecting tumor markers and imaging detection, which is should be done in the specific area—hospital, and under professional persons’ guidance.

Goals

However, it’s difficult for patients and doctors to easily and directly monitor the breast cancer and other tumors. We need the patient do some specific test in the hospital under the guidance of doctors. So, our team take a deep think about this phenomenon and want to make this process easier. So, we design a new way to monitor and kill tumor cells at the same time. (Take a look at details of our project).

Here, we design a synthetic immune system called Wukong.

This system contains three parts. First, we engineer detector cells to recognize specific biomarkers on tumor cells, initiating killing and informing the other cells. Second, subcutaneously injected tattoo cells receive signal molecules from detecting cells and respond by accumulation of chromoproteins, warning the onset or progress of tumor. And we can see the tattoo cells’ color change to determine the tumor basic condition. Third, engineered muscle cells release therapeutic antibodies into the blood to synergize with the detector cells. By secreting and receiving different signal molecules, these reprogrammed cells are able to communicate and cooperate with one another. To achieve this, the synthetic receptors and signal molecules are critical, so we designed and tested several types of them. We hope this system could perform a wide variety of functions against tumor, from monitoring, treatment to prevention of relapse and drug resistance.

Integrated human practices

Abstract

“Stakeholders” is defined as those who are directly or indirectly influenced by our project. From stakeholders, we can learn the most concrete and detailed knowledge about our project. For example, only those who underwent chemotherapy will understand how painful it is to vomit even after drinking a cup of water, and they will tell you their eagerness to have a new therapy without so many horrible side effects. Sometimes, conflict of interest is unavoidable between people holding different position. For those who have invested in millions of dollars, they need to get paid back. However, for those patients without enough money, it is impossible to afford those expensive medication, even it is the most effective one in the world. How to strike the balance is also a major issue in our project. We communicated with different people during our project, trying to understand their problems, comments, suggestions and advice. We also received complaints and appreciations. We asked their expectations about how to treat and monitor breast cancer. So that our project, WuKong, will be efficient, user-friendly and meet the patients’ needs in future.

Inspiration

In April 19, members of our team went to Henan Province to provide medical services and to promote synthetic biology at the same time. At that time, we met a patient with breast cancer, who told us about her bitter experience. Her treatment about breast cancer is very difficult and painful. What’s more, some members in our team are clinic medical students and in their internship in ChangZheng hospital, they also learned a lot of cancer cases and the difficulties of tumor treatment and surveillance, as what we said before in the OVERVIEW. So, we want to explore if there is another way to deal with tumor. Inspired by the wonder work of Sanjiv S. Gambhir, we want to design a new treatment system to monitor and kill cancer cells together. Since the breast cancer very common tumor among females, we choose it as our disease model. And under the guidance of professor Hu and professor Lei, our project contains two parts, detection/killing part and reaction/screening part based the synNotch receptor binding to HER2 and GEMS receptor binding to IL-15.

Interview with Professor Lu Jian

“Engineered NK cells with synthetic Notch Receptors” & “How to ensure biosafety and biocompatibility”

Prof. Lu Jian received her PhD from Osaka University in Japan in 1990. In the same year, she was promoted to our university’s professor. Now she is the director of the Department of Pathology. She really likes to exchange ideas about research with undergraduates.

After returning from Henan, we had several group meetings, discussing about advantages and disadvantages of CAR-T cells and CAR-NK cells. Both therapies have been proved as safe and effective in laboratory animals. In comparison, CAR-T cells therapy has been approved by FDA for investigational study way early in 2007, while CAR-NK cells therapy is a new idea remains to be explored. Despite the maturity of CAR-T cells, we decided to give CAR-NK cells a try. Thereafter, we went to visit professor Lu.

Engineered chimeric antigen receptors have been testified as a promising weapon against cancer. Current studies show that CAR-NK cells embraces better safety and effectiveness when compared with CAR-T cells. According to our design, the engineered cell must be capable of recognizing tumor cells, which is the most upstream part. Professor Lu suggested us to try synthetic Notch receptors and GEMs receptors, which has recently been recognized as a potential platform to recognize antigens of tumor cells. Synthetic Notch receptors allow NK cells to response completely independent, which means more diverse programming without interfering with endogenous system.

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Interview with Professor Liu Shanrong

“How to ensure biosafety and biocompatibility”

Dr. Liu Shanrong is the director of Changhai clinical laboratory. He has been committed to tumor detection research for many years and published some influential papers. He loves teaching of laboratory diagnostics and has a unique teaching model which is attractive to students.

In the last year, we have introduced our project to people with all kinds of background. The most frequently asked question is their concerns about implanting such an artificial equipment into their body. Is it safe to accept such a multi-functional cellular weapon implanted into human bodies? What if it causes a severe immune response, would that be a devastating blow for our health? To find the best solution for these questions and for our project, we consulted Professor Liu for advice.

When we completed the preliminary design of the project, we interviewed professor Liu and consulted him about how to improve our project and how to find a mature nanomaterial, professor Liu gave us lots of suggestions.

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Meeting with patients

“Therapy combined of genetic engineering and synthetic biology”

After our class, our teacher invited 2 patients to share their personal experience in fighting against cancer. The first patient was a 15-year-old girl, she was diagnosed with osteosarcoma 1 year ago. Tumor was on her left femur, so she lost her left leg during the osteosarcoma ectomy. Now she was accepting chemotherapy. She told us, although she had lost her leg and her hair, she would return to school as soon as her disease is cured. Another patient was an 80-year-old man with lung cancer. Tumor cell was detected in his lymph nodes, so he was not indicated for surgery. He was also accepting chemotherapy when we met him. He looked pale and weak. In contrast to that little girl, he was a pessimist, so fragile as a little boy, he told us that his only hope was to suffer less. Chemotherapy led to anemia, appetite loss, constipation, diarrhea, fatigue, hair loss, and every time he left hospital, an infection would strike at him.

What do we learn

bTumor cells have similar nature as stem cells, but they are far more aggressive. Patients with cancers will finally become cachexia, which means loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite because of the unlimited growth of neoplasm. We had a better understanding about side effects of different therapies for cancers after meeting with patients. Surgery is the best for patients without metastasis, but trauma or even amputation is sometimes a must. Chemotherapy and radiation therapy are widely applied, but damage to normal cells can lead to infection, hair loss, loss of appetite and so on. Other newly-invented therapies are of limited applications, their indications are narrow. Most important of all, early diagnosis and prevention are of more significance than treatment in our fight against cancers. If the old man could be diagnosed before any metastasis, there would be no better option than surgery. Thus, we decided to create a multi-function system, including detection, diagnosis, and automatic treatment. The professor recommended us to design our system based on combination of synthetic biology and cell therapy. According to him, chimeric antigen receptor therapy, a recent breakthrough in cell therapy, would be of great significance if we could really work something out. To edit cells based on certain logic and standard components for different usage is a meaningful recently-emerged idea, which hinges on combination of synthetic biology and cell therapy. However, one of the most challenging obstacles in curing cancers is the heterogeneity of even the same kind of cancer. Thus, he suggested us to focus on a certain type of cancer, since every cancer and its antigen is relatively specific. For example, over-expression of ERBB2 gene has been validated in breast cancer, but not in liver cancer. Our system has to specifically focus on a certain type of protein, and the professor advised us to focus on breast cancer since its mutation and target therapy has been widely accepted and proved.

Social media

Smartly choose suitable media to show the world about our project, iGEM and synthetic biology.

We created a platform based on WeChat, the most popular social media in China, to promote the publicity of our team, enhance the interaction between us and people interested in synthetic biology and our project, and popularize basic concept and knowledge of synthetic biology.

Games

Simple game, simple learning.

To promote Synthetic biology in an interesting way, we design a simple and funny game to help others better understand the gene circuit. In this game, we have four different cards which represents the promoter, transcription factor, operon and gene. And when we held summer camp, we show the high school students this game. They learnt it very quickly and played it happily. They said that it was an easy game to understand and learned that the basic parts in a gene circuit.