NEW YORK (Reuters Health) - In patients with metastatic gastrointestinal cancers, a feasibility study has shown that intratumoral injection of dendritic cells engineered to secrete interleukin-12 can safely be accomplished.
The technique, which combines genetic and cellular immunotherapy, is described along with a report of the study in the February 10 issue of the Journal of Clinical Oncology by Dr. Guillermo Mazzolini and colleagues at the University of Navarra in Pamplona, Spain.
The dendritic cells were generated from CD14-positive monocytes transfected with adenovirus encoding interleukin-12 genes and then administered by intratumoral injection to 3 patients with metastases from pancreatic cancer, 6 with spread of colorectal cancer, and 9 with metastatic liver cancer. The injections were guided either by ultrasound, endoscopy, or computed tomography.
“Treatment was well tolerated,” the researchers report, with lymphopenia, fever and malaise the most common side effects. There was no instance of dose-limiting toxicity or any evidence of long-term toxicity.
Biologic response included increased serum concentrations of interferon gamma and interleukin-6 in 15 patients and an increase in peripheral blood natural killer activity in 5 patients.
In addition, the authors report, the treatment “stimulated a potent antibody response against adenoviral capsids” along with “a marked increase of infiltrating CD8-positive T lymphocytes in three of 11 tumor biopsies analyzed.”
Among the 11 patients in whom antitumoral response was analyzed at day 63, one with pancreatic cancer had a partial response, two with hepatocellular carcinoma had stable disease, and the remaining 8 had tumor progression. Two of these 8 had disease described by the authors as “fast progressing during treatment.”
“Intratumoral injection of dendritic cells transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated,” the investigators conclude. “Further studies are necessary to define and increase clinical efficacy.”
Source: J Clin Oncol 2005;23:999-1010. [ Google search on this article ]
MeSH Headings:Biological Therapy: Digestive System Neoplasms: Gastrointestinal Neoplasms: Genetic Engineering: Genetic Techniques: Investigative Techniques: Neoplasms: Neoplasms by Site: Therapeutics: Gene Therapy: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
