TUSTIN, Calif. -- January 24, 1997 -- Vascular Targeting Agents (VTAs), a promising cancer therapy that interrupts the blood supply necessary for a solid tumor's continued survival, is the subject of a study published in the January 24 issue of Science, the weekly journal of the American Association for the Advancement of Science.
The study tested the selective occlusion of tumor vasculature as a therapy for solid tumors in a mouse model. The formation of blood clots (thrombosis) within the tumor vessels was initiated by targeting the cell surface domain of human tissue factor, by means of a bispecific antibody, to an experimentally induced marker on tumor vascular endothelial cells (the layer of flat cells that line tumor blood vessels). The intravenous administration of the antibody-tissue factor complex to mice with large neuroblastomas resulted in complete tumor regressions in 38 percent of the mice and a partial response rate (classified as greater than 50 percent decrease in initial tumor volume) of 24 percent.
"These results show an exciting, new approach to the treatment of large, solid tumors," said Dr. Philip Thorpe, Ph.D., a principle investigator in the study and the Serena Simmons Distinguished Chair of Cancer Immunopharmacology at the University of Texas Southwestern Medical Center in Dallas, Texas. Dr. Thorpe, a pioneer in the field of vascular targeting and scientific founder of Peregrine Pharmaceuticals, added "Because vascular targeting agents are highly specific and anchor to endothelial cells in contact with blood, considerably less drug is needed to achieve a therapeutic effect, thus providing a less toxic, yet highly effective therapy for solid tumor treatment." Peregrine Pharmaceuticals recently announced that it will be acquired by Techniclone Corporation (NASDAQ: TCLN), a cancer therapeutic company that is also pioneering treatment of solid tumors.
The study was designed based on the following principles:
- Since tumor cells depend on a blood supply to receive oxygen and nutrients for survival, the local interruption of the tumor vasculature causes massive tumor cell death;
- The endothelial cells, which are targeted, are in direct contact with the blood, whereas tumor cells are outside the bloodstream and are poorly accessible to immunoconjugates; and
- Tumor vascular endothelial cells are normal cells and thus are unlikely to acquire mutations that render them resistant to therapy.
Within 30 minutes after the clot-inducing drug was delivered via vascular targeting agents, all vessels throughout the tumor were blocked due to blood clots, which "starved" the tumor of oxygen and nutrients and resulted in massive tumor cell death. By 24 hours, the tumor showed advanced necrosis, and by 72 hours, the entire central region of the tumor had condensed into amorphous debris. Throughout this process, the treatment was well tolerated, and the mice lost no weight and retained a normal appearance and level of activity.
"Vascular targeting agents, because of their selectivity in targeting the tumor vessels and ability to not affect surrounding healthy tissues, represents one of the major advances in solid tumor therapy that will be the next generation of more humane cancer treatments," said Lon Stone, president and CEO of Techniclone Corporation.
A More Humane Cancer Treatment Approach
According to Dr. Alan Epstein, Ph.D., professor of pathology at the University of Southern California Medical Center and director of scientific affairs for Techniclone, "Innovative drug delivery systems that permit large, cancerous tumors to be destroyed without damaging surrounding healthy tissue may provide promise as a future front-line therapy for cancer patients."
Techniclone Corporation is leading the industry with two solid tumor therapies that are non-invasive, involve less toxicity, and result in fewer side effects for patients than with current chemotherapies -- Tumor Necrosis Therapy (TNT) and Vascular Targeting Agents (VTAs). These proprietary technologies are designed to be effective across a broad spectrum of solid tumors larger than 2 mm in size, including lung, colon, breast, prostate, pancreatic and brain cancers.
Tumor Necrosis Therapy (TNT) uses a monoclonal antibody which carries toxic "payloads" (such as radioisotopes) directly to the inner core of large, cancerous tumors. Preclinical trials have shown that once TNT is injected into the blood stream, it acts like a guided "smart bomb," anchoring to antigens on the DNA within the nucleus of the cell and delivering the radioactive payload specifically to the inside of the tumor--destroying the tumor from the inside-out.
Future Collaboration Of Therapies
Cancer cells, unlike normal tissues, undergo rapid degeneration resulting in areas of necrosis (dead tissue) where the cell membrane is "leaky" and porous--allowing large molecules (like antibodies) to penetrate the cell. Scientists at Techniclone are currently testing the combination of VTAs and TNT in animals with large, solid tumors, and expect to enter TNT into human trials later this year.
Since the DNA-associated antigens, to which TNT anchors to, only become accessible in dead cells, by first administering VTAs (and causing massive tumor cell death), TNT can become even more effective by creating a larger "target area" into which TNT can deliver its payload and kill any remaining live tumor cells (on the outer tumor) that survived the VTA therapy.
"The synergistic opportunities of these two technologies offering enhanced effectiveness is exciting," said Dr. Thorpe. "Although the two technologies provide for swift and targeted tumor cell death as individual therapies, together, they represent the potential for a powerful 'one-two' punch in future cancer treatments. The efficiency of these two drug delivery platforms may one day provide a more humane treatment for all solid tumor cancer patients."
Portfolio Of Products For Future Cancer Treatments
Established in 1981 and headquartered in Tustin, Calif., Techniclone
Corporation's most advanced drug development program is LYM-1, a non-Hodgkin's
B-cell lymphoma therapy product currently being studied in a multi-center U.S.
Phase II/III clinical trial. In addition to the TNT product (U.S. clinical
trial scheduled to begin in 1997), the company is also planning for clinical
trials for its patented Vasopermeation Enhancement and Vascular Targeting Agents
products. Additional corporate and product pipeline information can be obtained
on Techniclone Corporation's Internet web site (http://www.
This release contains certain forward-looking statements that involve a number of risks and uncertainties. Actual events or results may differ from the company's expectations as a result of the risk factors discussed in Techniclone's reports on file with the U.S. Securities Exchange Commission (including, but not limited to, the report on Form 10-Q for the quarter ended October 31, 1996).