Researchers are well on their way to developing vaccines that could stop the spread of cancer cells to other locations in the body-the main roadblock to curing cancer.
An international team of scientists already has conducted highly successful animal tests of the vaccines and is ready to move on to human trials.
The vaccines have proved effective in stimulating animals` immune systems to destroy free-floating cancer cells, thereby blocking the spread, or metastases, of the original cancer, said molecular biologist Eli Gilboa of Memorial-Sloan Kettering Cancer Center in New York.
Gilboa and Dr. Bernd Gansbacher, a cancer specialist at Memorial-Sloan Kettering, are collaborating with Dr. Michael Feldman, chief of cell biology at the Weizmann Institute of Science in Rehovath, Israel, to develop human cancer vaccines using genetically engineered cancer cells.
The cells are irradiated to destroy their ability to cause cancer. New genes are inserted into the cells to ``hypersensitize`` the immune system and enable it to overcome the capacity of some cancer cells to hide from the body`s natural defenses and set up new colonies.
The altered cancer cells then are returned to the patient.
``The ability of these tumor vaccines to stop the spread of cancer in mice is amazing,`` Gilboa said. ``A number of research groups are gearing up to do phase 1 clinical trials.``
Phase 1 trials test the safety of a new therapy in human beings, and it may be several years before the safety and effectiveness of the cancer vaccines can be established. Memorial-Sloan Kettering in New York and M. D. Anderson Hospital and Tumor Institute in Houston are planning clinical trials but have not set a date to begin. It has not been determined how many people will be involved.
Because the vaccines involve a form of gene therapy, the studies must be approved by a special committee of the National Institutes of Health before human experiments can begin. A proposal is expected to be presented soon.
In experiments in animals, Feldman has shown that the primary way cancer cells evade surveillance and destruction by the immune system is to hide their antigens, or chemical identification cards, which normally sit on the surface of cells.
White blood cells of the immune system are constantly on the lookout for antigens, which are found on bacteria, viruses and cancer cells. When an antigen is discovered, the immune system is alerted to muster its forces and then destroy tumor cells.
Some cancer cells escape detection by pulling in their antigens, like retracting a car antenna, making them invisible to the immune system, Feldman explained.
``If cancer cells did not metastasize, cancer would be a very curable disease,`` he said. ``It could be easily cut out, irradiated or destroyed with drugs.``
But by the time the original cancer is detected, some tumor cells already may have broken free and established secondary cancers at distant sites, he said. As a result, therapies often fail to destroy all the cancer cells and new malignancies flare up, he said.
Dr. Carlos Cardon-Cardo, head of Memorial-Sloan Kettering`s molecular immunopathology laboratory, said studies conducted with researcher Zvi Fuks showed human tumors contained some cancer cells that had pulled in their antigens to hide from the immune system.
Cardon-Cardo also found some of these stealth-like cancer cells were free-floating in the blood stream.
``They circulate like ghost cells that the immune system can`t see and attack,`` he said.
Cells that metastasize are masters of survival, Feldman said. During metastases they first must break free from the parent cancer. Then they must punch a hole in a blood vessel to enter the blood stream, float undetected through the blood, stop at an appropriate target organ, punch out of the blood stream and secrete signals that stimulate the growth of tiny blood vessels to feed them.
``The key to metastases is the ability of the cancer cell to hide from the immune defenses in the bloodstream,`` Feldman said. ``If they could not hide, the immune system would find them and destroy them.``
To make cancer cells visible to the immune system Feldman inserted a gene called H2K into metastasized mouse cancer cells that had been irradiated to kill their cancer-causing potential.
The H2K gene is responsible for producing cancer antigens. The gene is so weak in metastasized cancer cells that very little antigen is made and the cells escape detection by the immune system. Feldman`s strategy is to put the H2K-reinforced cells back into patients` bloodstreams so that their immune systems become much more sensitive to the low level of antigens on the malignant cells.
When Feldman gave his vaccine to mice that had been injected with highly metastatic lung cancer cells, he said the immunity produced by the vaccine prevented the tumor from spreading.