VANCOUVER, British Columbia - Inex Pharmaceuticals Corp. has reported its gene therapy, INXC-gTK, has the ability to shrink tumors in mice.
The news follows closely on the heels of the establishment of a multiyear research collaboration deal with Sequitur Inc., of Natick, Mass., involving antisense drug development. (See BioWorld International, May 27, 1998, p. 1.)
The latest data were reported at the American Society of Gene Therapy Conference, in Seattle. The company demonstrated in an animal model that its transmembrane carrier systems (TCS) drug delivery technology confers protection from degradation in the body and allows a therapeutic payload to be effectively delivered to distal cancer tumor sites.
Pieter Cullis, vice president of Research at Inex, said efficacy studies examined intravenous administration of INXC-gTK encapsulated with TCS and its effects on fibrosarcoma tumors induced in the rear flanks of mice. Five days after the induction of tumor, the mice received injections of INXC-gTK with ganciclovir (GCV), the off-patent antiviral drug.
Assessment of tumor growth was made after 20 days. It was found that the size of the tumors was significantly reduced after intravenous treatment with the drug combination. Groups treated with GCV alone or with an unrelated gene did not have any noticeable effect on tumor size. In addition, the results of INXC-gTK administration did not reveal any of the adverse toxicities normally encountered with conventional cancer chemotherapeutic drugs, Cullis added.
The studies show the thymidine kinase gene (TK) is being delivered effectively to distal tumor sites by TCS. Once inside the cells, the TK gene synthesizes a protein that is able to convert GCV into a toxic form that destroys the cancer cells.
Approach Bodes Well For Antisense
The results are encouraging for antisense drugs, which usually are active only inside target cells. The problem has been how to deliver them there. As these drugs are large molecules, they tend to be degraded rapidly in the bloodstream and have difficulty penetrating cell membranes.
Research results to date using other gene delivery technologies, such as lipid complexes and viruses, have reported limited success in the ability to carry genes beyond the lungs and liver after systemic administration. These limitations have restricted the majority of cancer gene therapy research to direct injection or local delivery of the gene to the tumor site.
The TCS capsule that confers protection to therapeutic drugs is a proprietary mixture of specific lipids and, for certain applications, detachable polymers that enhance stability and regulate the circulation time of the therapeutic agent.
Cell-specific targeting of TCS makes use of ligands, such as vitamins, that are incorporated into the TCS membrane. Once at the target cell the TCS fuses with its outer membrane so the therapeutic agent can pass into the cell.
The company says it will ramp up its follow-up studies over the next few months, and if these show as much promise as the current animal data, human clinical trials will be initiated for INXC-gTK. *