Introgen Therapeutics Inc reported that INGN 241, its second clinical product, has antitumor activity by two independent mechanisms: by activating the immune system to kill cancer cells and by directly inducing apoptosis in those cells.

These data were described in two oral presentations at the 11th International Conference on Gene Therapy of Cancer, recently held in San Diego, Calif. These data mirror preclinical studies also presented at the conference, which showed evidence of immune-system stimulation and apoptosis induction.

The first talk, presented by Alex Tong, of Baylor Sammons Cancer Center and U.S. Oncology, described the immune-system stimulating effects of INGN 241 (Abstract # 97). After treatment with INGN 241, a majority of patients experienced transient increases in a number of important cytokines, ranging from 150 to 1540% of pretreatment levels; cytokines play important roles in immune system function and in regulating cells. Levels of certain immune cells known as cytotoxic/killer T-cells were also increased. Killer T-cells are thought to play an important role in controlling cancer and infectious diseases. It is expected that these immune responses will augment the ability of the INGN 241 gene drug to kill cancer cells in the local tumor environment by acting systemically.

"INGN 241 appears to act via a unique combination of tumor-specific apoptosis and immune activation," said Dr. Tong. "We expect that these two different anti-cancer mechanisms will complement each other and result in destruction of INGN 241-injected as well as distant tumors. Furthermore, this novel gene drug may provide benefit to patients with various types of cancer."

The clinical data are derived from a phase 1 study in which patients with advanced cancer received single doses of INGN 241. INGN 241 incorporates the mda-7 gene in Introgen's adenovirus vector. The study was designed to look at the safety and biological effects of INGN 241 delivered intratumorally at a range of doses. Investigators wished to explore what effects INGN 241 treatment of human tumors might have on various components of the immune system, including cytokines and certain cells. To accomplish this, they measured the levels of a range of cytokines in plasma, along with certain common immune cells, just before and for several weeks following treatment with INGN 241. Then, the tumors were removed to determine direct effects. The only toxicities observed in the study were injection-site pain and occasional low-grade fever, suggesting a favorable safety profile. The study ultimately showed that advanced solid tumors, including breast, colorectal, melanoma and lymphoma, all take up this gene drug efficiently, resulting in high levels of MDA-7 expression and apoptosis induction in tumor cells. The molecular analyses complement the positive safety profile and provide impetus to further explore the therapeutic value of this gene drug.

The mda-7 gene was first discovered by the laboratory of Dr. Paul B. Fisher, Professor of Clinical Pathology and the Michael and Stella Chernow Urological Cancer Research Scientist in the Departments of Neurological Surgery, Pathology and Urology at Columbia University. Introgen holds an exclusive worldwide license to the gene for all gene therapy applications from the Corixa Corporation.