Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Recurrence

Brain Neoplasms

Neoplasm Metastasis

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Anti-Infective Agents

All Drugs and Chemicals

Ganciclovir

Ganciclovir triphosphate

Antiviral Agents

Enzyme Inhibitors

Cytovene (Ganciclovir Sodium)

G1TKSVNa.53 Producer Cell Line

Malignant brain tumors are responsible for a significant amount of deaths in children and adults. Even with advances in surgery, radiation therapy, and chemotherapy, many patients diagnosed with a malignant brain tumor survive only months to weeks.

In an attempt to improve the prognosis for these patients, researchers have developed a new approach to brain tumor therapy. This approach makes use of DNA technology to transfer genes sensitive to therapy into the cells of the tumor.

Infections with the herpes simplex virus can cause cold sores in the area of the mouth. A drug called ganciclovir (Cytovene) can kill the virus. Ganciclovir is effective because the herpes virus contains a gene (Herpes-Thymidine Kinase TK gene) that is sensitive to the drug. Researchers have been able to separate this gene from the virus.

Using DNA technology, researchers hope to transfer and implant the TK gene into tumor cells making them sensitive to ganciclovir. In theory, giving patients ganciclovir will kill all tumor cells that have the TK gene incorporated into them.

Malignant brain tumors are responsible for significant morbidity and mortality in both pediatric and adult populations. These common tumors present an enormous therapeutic challenge due to their poor outcome despite radical surgery, high dose radiotherapy and chemotherapy. Survival of patients from the time of diagnosis is measured in months and recurrence after treatment is associated with a life expectancy of weeks.

In an attempt to improve this grim prognosis of patients with malignant brain tumors (both primary tumors and secondary metastasis from systemic cancer such as melanoma, lung and breast cancer), we developed a novel approach to the therapy of brain tumors. This approach makes use of recombinant DNA technology to transfer a sensitivity gene into a brain tumor. This is achieved by direct injection of the tumor with a cell line actively producing a retroviral vector carrying a gene conferring drug sensitivity to the tumor. A retroviral vector is a mouse retrovirus genetically engineered to replace its own genes with a new gene. Such vectors are capable of "infecting" mammalian cells and stably incorporate their new genetic material into the genome of the infected host. The producer cell is an NIH 3T3 cell that has been genetically engineered to continually produce retroviral vectors. The new gene is incorporated into the genome of the tumor cells and expresses the protein which is encoded by the new gene. This protein (the herpes simplex virus enzyme thymidine kinase, HS-tk) sensitizes the tumor cells to an antiviral drug (ganciclovir, GCV) which is a natural substrate for HS-tk. The enzymatic process induced by GCV leads to death of a natural substrate for HS-tk. The enzymatic process induced by GCV leads to death of the cell expressing the herpes TK activity, i.e., death of the tumor cells. Since the HS-tk enzyme which is normally present in mammalian cells has very low affinity for GCV, systemic toxicity related to this mechanism is not observed. This type of in vivo gene transfer has several unique features. First, these retroviral-vectors will only integrate and express their genes in cells which are actively synthesizing DNA. Therefore, surrounding non-proliferating normal brain tissue should not acquire the HS-tk gene and will remain insensitive to GCV. Second, all of the transduced tumor cells (and retroviral vector producing cells) will be killed by the host immune response and/or GCV treatment eliminating potential concern about insertional mutagenesis giving rise to malignant cells.

This is the first clinical attempt to treat malignant tumors in human beings by in-vivo genetic manipulation of tumor's genome.

Gene Therapy for the Treatment of Brain Tumors

Gene Therapy for the Treatment of Brain Tumors Using Intra-Tumoral Transduction With the Thymidine Kinase Gene and Intravenous Ganciclovir

National Institute of Neurological Disorders and Stroke (NINDS)

John D. Heiss, M.D./National Institute of Neurological Disorders and Stroke

Radiofrequency tumor ablation (RFA) is an imaging guided percutaneous or intra-operative procedure that uses a probe on the end of a sharp needle that is inserted directly into the tumor. The tumor is ablated by heating the probe (using electrical current alternating at radio frequency) which raises the temperature of the tumor potentially causing irreversible cell death.

Radiofrequency Tumor Ablation

Matthew Krasin, MD

Background: This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors.

Methods: From 2003 through 2006, we conducted a phase I, IRB-approved study of RFA for recurrent solid tumors. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging-guided RFA was performed percutaneously. Response was assessed at 3 months. Repeat RFA was performed for some incompletely ablated or new lesions.

Radiofrequency Ablation of Tumors

Radiofrequency Ablation of Tumors (RFA) A Phase I Study

St. Jude Children's Research Hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gene Therapy for the Treatment of Brain Tumors	NCT00001328	Brain Neoplasm Neoplasm Metast...	Cytovene (Ganci... G1TKSVNa.53 Pro...	19 Years -	National Institutes of Health Clinical Center (CC)
Radiofrequency Ablation of Tumors	NCT00705497	Primary Tumors Metastatic Tumo...	Radiofrequency ...	-	St. Jude Children's Research Hospital
Gene Therapy for the Treatment of Brain Tumors	NCT00001328	Brain Neoplasm Neoplasm Metast...	Cytovene (Ganci... G1TKSVNa.53 Pro...	19 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for primary tumors