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Cancer gene therapy update

National Institutes of Health Clinical Center Pharmacy Department, Bethesda, Maryland

Barry R Goldspiel, PharmD, FASHP

National Institutes of Health Clinical Center Pharmacy Department, Bethesda, Maryland

Objective. To provide an update about gene marking and gene therapy trials in cancer patients.

Data Sources. A MEDLINE search using the term "gene therapy" was conducted for the period 1985 to 1998. The reference lists from retrieved articles were reviewed. Meeting abstracts from the American Society of Clinical Oncology annual meeting (published in their proceedings) and the Annual Cancer Gene Therapy Symposium (published in Cancer Gene Therapy) that concerned gene therapy in cancer patients were also included.

Data Extraction. Both authors reviewed the retrieved material and included preclinical data, case reports, and clinical trials related to gene transfer or gene therapy in cancer patients.

Data Synthesis. There are several possible approaches to using gene therapy for the diagnosis and treatment of cancer and for the monitoring of cancer therapy. Exogenous genes may be used to mark cells to help better understand cancer biology or may be used directly for cancer treatment. Gene-marking trials have already provided new information about cancer biology and have demonstrated that reinfused progenitor cells may be a source of relapse in patients with acute or chronic myelogenous leukemia and neuroblastoma.

Approaches using gene therapy for cancer treatment include: using lymphocytes as gene carriers, using foreign genes to increase tumor immunogenicity, introducing tumor regression antigen genes into viruses, introducing "sensitivity" genes to produce new cytotoxic agent(s) within tumors, producing new protein product(s) to protect normal cells, replacing missing or mutant tumor suppressor genes, and inactivating oncogenes. Clinical trials using these strategies have demonstrated that gene transfer is feasible (albeit with low transduction efficiency) and that gene expression occurs; in addition, clinical responses have been noted.

Key Words: Gene therapy • gene transfer • retroviral vector • cancer • tumor targeting

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