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Gene Therapy (Gendicine)


China is the only country in the world where gene therapy is developed and licensed by the SFDA (State Food and Drug Administration) to be practiced since 2004. 

What is Gene Therapy? 

Gene therapy targets the root of the disease by correcting the abnormal gene. Gene therapy is the process of replacing defective or cancerous genes (also called “oncogenes”) with normal genes. The removal of these oncogenes reprograms the cell to its normal state, preventing tumor growth and the spread of cancer.  

Why is tumor a group of genetic diseases? 

Cancer is a group of diseases in which the body's normal self-regulatory mechanisms no longer control the growth of some kinds of cells. Cells are frequently exposed to a variety of agents, from both external and internal sources, which damage DNA. Even minor DNA damage can have profound effects, causing certain genes to become overactive, to undergo partial or complete inactivation, or to function abnormally. Genes control a number of protective pathways in cells that prevent cells from becoming cancerous. For example, pathways that transmit signals for a cell to divide have on-off switches that control cell division. Cells also have mechanisms that allow them to determine if their DNA has been damaged, and they have pathways to repair that damage or eliminate the cell. The failure of any of these protective pathways can lead to the development of cancer.  


Recombinant Human Ad-p53 Injection (Gendicine), developed after more than five years of laborious clinical trials, is a drug that can be injected into the patient to change the p-53 gene. Following the successful completion of clinical trial I, numerous doctors and nurses led by Professor Zhang Shanwen of the Beijing Cancer Hospital have favorably finished clinical trial II on head and neck squamous cell carcinoma (HNSCC). This confirms that Gendicine is safe and effective for HNSCC. The drug license was issued on October 16th, 2003 by the State Food and Drug Administration of China, which means the world’s first anticancer gene therapy drug was born in China.

Gendicine is an infectious, replication-incompetent, engineered recombinant human adenoviral particles (rAd/p53), composed of the adenoviral vector and the human wild-type p53 tumor suppressor gene. Gendicine uses an adenoviral vector to carry p53 tumor suppressor genes into tumor cells. It is widely believed that p53 is the most powerful gene known to curb the genetic expression of tumor cells. In combination with chemo- and radiotherapy, Gendicine has improved treatment efficacy more than 3-fold. HNSCC predominantly strikes men after age 50, and until now prognosis for survival had been poor, despite combined surgery and chemotherapy or radiation therapy. Gendicine will provide hope to about 300,000 new patients in China who are diagnosed with this malignancy each year.

How does Gendicine fight cancer? 

Gendicine's functional component is the p53 gene, a naturally occurring tumor suppressor gene that has been under research in the United States, Europe and Asia for 20 years. The p53 gene exists ubiquitously in normal cells and is one of the most prevalent tumor suppressor genes in the human body. In the medical establishment, its unique properties have earned it the nickname, 'Genome Guardian.'


The exact mechanism by which p53 attacks cancerous growths is still under debate, but it appears to exert its anti-tumor activities using one or more of the following mechanisms:


1.By causing self-destruction of the cancerous cells

The p53 gene simultaneously triggers self-destructive pathways (apoptosis) in tumor cells by a transcription-independent mechanism in the cell nucleus and by a transcription-independent mechanism in the mitochondria (the cells energy production facility) and Golgi apparatus (a system of membranes and tubes involved in intercellular transport).


2.By alerting neighboring 'killer' cells to the presence of cancerous ones

The gene can activate certain immune response factors such as natural killer (NK) cells to exert 'bystander effects'.


3.By preventing the tumor's cellular self-management

Inhibiting the cancerous cell's DNA repair and anti-apotosis functions, p53 hinders the development of tumors.


4.By inhibiting the defense and propagation mechanisms of the tumor

The p53 gene limits (1) multi-drug resistance genes which make tumor cells more immune to radio- and chemotherapy, (2) the tumor's ability to generate blood flow around itself (see also Anti-angiogenesis Therapy) and (3) matrix metalloproteinase (MMP), a substance which promotes tumor cell adhesion, infiltration and metastasis (multiplication and spreading of small tumors).


5.By interfering with inter-cellular communication

Through blockage of the transcription of survival signals in tumor cells, p53 thus inhibits the growth of tumor cells in any stage of the cell cycle.


6.By hindering the cancerous cell's nutrient acquisition

Limitation of the uptake of glucose and the production of ATP (the cell’s energy supply) hinders tumor cell function. 


Clinical studies of Gendicine


Phase I of the clinical trials of intratumoral administration of Gendicine in patients with laryngeal squamous cell carcinoma was completed in Beijing Tongren Hospital. The results indicated that the main side effect was fever at a dose of 1×1012VP (virus particles). Thusly, the recommended dosage that should be adopted in phase II is 1×1012VP/injection/week.


By November 2005, (4-6 years after initial testing) of the 12 patients who participated in phase I, 11 patients survived with a median time of 5.9 years.


A multicenter, randomized, open-label, parallel design phase II/III clinical trial was conducted in which patients with head and neck squamous cell carcinoma (HNSCC), the majority of whom also had nasopharyngeal cancer, were divided randomly into two groups. One group received gene therapy in combination with radiotherapy (GTRT) and the other group received radiotherapy alone (RT). There were no significant differences (p>0.05) in age, sex, or clinical stage, or in size of tumor lesion between the two groups of patients. Conventional or three-dimensional conformal radiotherapy was used at doses of 70 Gy (a unit of radiation absorption) administered in 35 fractions over 7–8 weeks for the RT group. For the GTRT group, Gendicine was given each week at a dose of 1×1012 VP 3 days before radiotherapy, for a total of 8 weeks. Radiotherapy in the GTRT group was the same as that used in the RT group. Objective tumor response was evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) according to tumor response criteria defined by the World Health Organization (WHO). The data showed that the response rate in the GTRT group was 93%, with 64% showing complete regression (CR) and 29% partial regression (PR). The response rate in the RT group was 79% with 19% of the patients showing CR and 60% PR. There is a significant difference (p<0.01) between the two groups in terms of both the CR rate and the PR rate. The CR rate in the GTRT group was 3-fold higher than that in the RT group. These results imply that Gendicine in combination with radiotherapy exhibits anti-carcinogenic effects.


By September 2005, the follow-up was carried out for 78 patients who participated in the phase II/III clinical trial including 40 cases in the GTRT group and 38 cases in the RT Group. The mean follow-up time was 39.4 months. The results showed that the median disease-free survival time, 3-year disease-free survival rate and 3-year overall survival rate are 38 months, 74.3% and 78.8% respectively in the GTRT group and 32 months, 61.7% and 69.4% in the RT group. The results are tabulated below.


Results Table


Gendicine is safe

  • The viral vector engaged in Gendicine is the first generation engineered replication-incompetent human adenovirus serotype 5. Gendicine will not replicate in the infected cells and is incapable of multi-cycle infection and of spreading to the neighboring cells. Therefore, Gendicine will not cause horizontal adenovirus infection or environmental contamination. More importantly, infected adenoviral DNA will not integrate into the human host cell genome. Consequently, Gendicine poses no genetic toxicity.
  • The clinical trial of p53 gene therapy has been in progress for more than 8 years, and about 5000 doses of rAd-p53 products (for example, Advexin, Gendicine) have been administrated. No severe side effects attributed to rAd-p53 gene therapy were observed.
  • The most prominent observed side effect is self-limited fever; in nearly 80% of the cases, temperatures ranged from 37.5 to 39.5 occurring usually 2 to 4 hrs after administration and lasting for approximately 2 to 6 hrs. The fever tends to diminish spontaneously and without medical intervention. Generally, fever occurs at the beginning of the treatment, and then decreases gradually in severity and incidence. Other rare side effects include chills, pain at the injection site, discomfort, fatigue, nausea, and diarrhea. Usually, no special management is needed as the symptoms vanish automatically. However symptomatic treatment may be employed according to circumstances. No increase in the side effects that are commonly caused by radiotherapy or chemotherapy were observed when used in combination with Gendicine. No allergic reaction has been observed.


Clinical Study Reference 

1. The antitumorigenic efects of wildtype p53 on human colon adenocarcinoma cells. Yuan Wenbin Zheng Shu, et al., Zhejiang Medicine. 2006, 28(1): 19-21


2. A preliminary clinical study on p53 gene in the therapy of advanced hepatocellular carcinoma. CHEN Shi-xiCHEN Jun et al., J. Intervent. Radiol. 2007, 16(2):127-129

3. Adenovirus mediated p53 gene therapy for human hepatocellular carcinoma. ZHANG Qin—hong WANG Don, et al., ACTA ACADEMIAE MEDICINAE MILITARIS TERTIAE. 2006,28(2):121-124

4. p53 Gene therapy combining with TACE for treatment of advanced hepatobiliary short·time follow-up in 15 cases. Chinese Medica1 Research&Clinica12008,6(4):12-14