Gendicine (Ad-p53), The First Approved Gene Therapy Product for Cancer: 12 Years in the Clinic
Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration (CFDA) as a first-in-class gene therapy product to treat head and neck cancer, and entered the commercial market in 2004.
Gendicine is a biological therapy that is delivered via minimally invasive intratumoral injection, as well as by intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed by Gendicine-transduced cells is a tumor suppressor that is activated by cellular stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis, senescence, and/or autophagy, depending upon cellular stress conditions.
Gendicine is a biological therapy that is delivered via minimally invasive intratumoral injection, as well as by intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed by Gendicine-transduced cells is a tumor suppressor that is activated by cellular stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis, senescence, and/or autophagy, depending upon cellular stress conditions.
Based on 12 years of commercial use in >30,000 patients (10% of whom are from outside of China), and >30 published clinical studies, Gendicine has exhibited an exemplary safety record, and when combined with chemotherapy and radiotherapy has demonstrated significantly higher response rates than for standard therapies alone. Overall, Gendicine treatment has produced total response rates (CR + PR) ranging from 90% to 96% in various clinical studies, consistent with the results of the phase II and phase III clinical trials that formed the basis for China FDA approval.
In addition to head and neck cancer, Gendicine has been successfully applied to treat various other cancer types such as lung, breast, cervical, ovarian, liver, pancreatic and at different stages of disease.
Thirteen published studies that include long-term survival data showed that Gendicine combination regimens yield progression-free survival times that are significantly longer than standard therapies alone. Although the p53 gene is mutated in >50% of all human cancers, p53 mutation status did not significantly influence efficacy outcomes and long-term survival rate for Ad-p53-treated patients.
To date, Shenzhen SiBiono GeneTech has manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements, and 169,571 vials (1.0 × 1012 vector particles per vial) have been used to treat patients. No serious adverse events have been reported, except for vector-associated transient fever, which occurred in 50–60% of patients and persisted for only a few hours. The manufacturing accomplishments and clinical experience with Gendicine, as well as the understanding of its cellular mechanisms of action and implications, could provide valuable insights for the international gene therapy community and add valuable data to promote further developments and advancements in the gene therapy field.
Wei-Wei Zhang, Longjiang Li, Dinggang Li, Jiliang Liu, Xiuqin Li, Wei Li, Xiaolong Xu, Michael J. Zhang, Lois A. Chandler, Hong Lin, Aiguo Hu, Wei Xu, and Dominic Man-Kit Lam.The First Approved Gene Therapy Product for Cancer Ad-p53 (Gendicine): 12 Years in the Clinic.Human Gene Therapy.Feb 2018.160-179.
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