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New horizons: gene therapy for cancer
1Hopital General Universtari Vall d'Hebron, Servico de Oncologia Medica, Barcelona, Spain. baselg@hg.vhebron.es
Abstract:
p53 gene mutations appear in numerous human cancers and are associated with anumber of cellular mechanism changes including a lack of apoptosis. Repeated intratumoral injection of the adenoviral p53 vector (Ad5CMV-p53) in patients with non-small cell lung cancer and head and neck cancer is feasible and well tolerated. Treatment results in expression of the p53 transgene and evidence of increased apoptosis. Dose-related antitumor activity has been seen in phase I trials in both lung and head and neck cancer. Transgene expression appears to occur even in patients who mount an immune response to the adenoviral vector. The evidence to date indicates that gene transfer can occur without contamination of health care workers by the vector. There is preliminary clinical evidence suggesting that the in vivo synergy seen between Ad5CMV-p53 and cisplatin may also occur in patients. Phase II trials are justified and have been started.
Insights
Gene therapy using the adenoviral p53 vector (Ad5CMV-p53) is safe and effective for treating lung and head and neck cancers. This p53 gene therapy increases cancer cell death and shows promising antitumor activity.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- p53 gene mutations are common in human cancers, leading to reduced apoptosis.
- Adenoviral p53 vector (Ad5CMV-p53) offers a potential therapeutic strategy for cancers with p53 mutations.
Purpose of the Study:
- To evaluate the feasibility, safety, and efficacy of Ad5CMV-p53 gene therapy in patients with non-small cell lung cancer and head and neck cancer.
- To assess transgene expression, apoptosis induction, and antitumor activity following Ad5CMV-p53 administration.
Main Methods:
- Repeated intratumoral injections of Ad5CMV-p53 were administered to patients.
- Feasibility, tolerability, transgene expression, apoptosis, and antitumor responses were monitored.
- Immune responses to the adenoviral vector and potential vector contamination were assessed.
Main Results:
- Intratumoral Ad5CMV-p53 injection was feasible and well tolerated in both cancer types.
- Treatment led to p53 transgene expression and increased apoptosis in tumor cells.
- Phase I trials demonstrated dose-related antitumor activity in lung and head and neck cancers.
- Transgene expression was observed even in patients with an immune response to the vector.
- No evidence of vector contamination of healthcare workers was found.
- Preliminary data suggest in vivo synergy between Ad5CMV-p53 and cisplatin.
Conclusions:
- Ad5CMV-p53 gene therapy is a safe and feasible treatment for non-small cell lung and head and neck cancers.
- The therapy effectively induces p53 transgene expression and apoptosis, leading to antitumor effects.
- Further investigation in Phase II trials is warranted due to promising preliminary results and potential synergy with chemotherapy.