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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Clinical utility of recombinant adenoviral human p53 gene therapy: current perspectives
Guang-Xia Chen1, Shu Zhang2, Xiao-Hua He1
1Department of Gastroenterology, First People's Hospital of Xuzhou, Xuzhou, Jiangsu Province, People's Republic of China.
Abstract:
Gene therapy has promised to be a highly effective antitumor treatment by introducing a tumor suppressor gene or the abrogation of an oncogene. Among the potential therapeutic transgenes, the tumor suppressor gene p53 serves as an attractive target. Restoration of wild-type p53 function in tumors can be achieved by introduction of an intact complementary deoxyribonucleic acid copy of the p53 gene using a suitable viral vector, in most cases an adenoviral vector (Adp53). Preclinical in vitro and in vivo studies have shown that Adp53 triggers a dramatic tumor regression response in various cancers. These viruses are engineered to lack certain early proteins and are thus replication defective, including Gendicine, SCH-58500, and Advexin. Several types of tumor-specific p53-expressing conditionally replicating adenovirus vectors (known as replication-competent CRAdp53 vectors) have been developed, such as ONYX 015, AdDelta24-p53, SG600-p53, OBP-702, and H101. Various clinical trials have been conducted to investigate the safety and efficiency of these adenoviral vectors. In this review we will talk about the biological mechanisms, clinical utility, and therapeutic potentials of the replication-deficient Adp53-based and replication-competent CRAdp53-based gene therapy.
Insights
Gene therapy using p53-based adenoviral vectors (Adp53) shows significant promise for cancer treatment. This review explores the mechanisms, utility, and potential of both replication-deficient and replication-competent Adp53 gene therapies.
Area of Science:
- Oncology
- Gene Therapy
- Virology
Background:
- Gene therapy offers a promising approach for cancer treatment by restoring tumor suppressor genes or inhibiting oncogenes.
- The p53 tumor suppressor gene is a key target for gene therapy due to its critical role in cell cycle regulation and apoptosis.
- Adenoviral vectors (Adp53) are frequently used to deliver therapeutic genes, demonstrating significant tumor regression in preclinical studies.
Purpose of the Study:
- To review the biological mechanisms, clinical utility, and therapeutic potentials of p53-based gene therapy for cancer.
- To discuss both replication-deficient and replication-competent adenoviral vector strategies for p53 gene delivery.
- To highlight the advancements and ongoing clinical investigations in Adp53 gene therapy.
Main Methods:
- Review of preclinical in vitro and in vivo studies on Adp53 efficacy.
- Analysis of engineered replication-deficient adenoviral vectors (e.g., Gendicine, Advexin).
- Examination of tumor-specific, conditionally replicating adenovirus vectors (CRAdp53) (e.g., ONYX 015, H101).
Main Results:
- Preclinical studies show Adp53 induces substantial tumor regression across various cancer types.
- Replication-deficient Adp53 vectors have demonstrated safety and efficacy in early trials.
- Conditionally replicating CRAdp53 vectors are being investigated for enhanced tumor selectivity and oncolytic activity.
Conclusions:
- Adp53-based gene therapy represents a significant advancement in antitumor strategies.
- Both replication-deficient and replication-competent Adp53 vectors hold considerable therapeutic potential for diverse cancers.
- Ongoing clinical trials are crucial for validating the safety and efficacy of these adenoviral gene therapies.
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