In an experiment that could revolutionize cancer therapy, medical researchers announced Monday that they will inject into malignant tumors new genes designed to trick the human body into destroying the tumors.
The direct injection of genes into tumors is the ultimate, streamlined version of gene therapy and differs drastically from existing methods. Those involve removing cells from patients, growing the cells in the laboratory,
``infecting`` the cells with viruses carrying the therapeutic gene, and finally returning the modified cells to the body.
Sometime in the next two months, twelve patient-volunteers dying of metastatic melanoma, the most lethal form of skin cancer, will receive direct injections of genes designed to trigger an immune response and hopefully kill the cancer. Most of the patients are not expected to live more than six months without the new approach.
``Direct gene transfer will facilitate the application of gene therapy to human disease,`` said Dr. Gary Nabel, chief of the University of Michigan team that will conduct the research. ``If this method of gene delivery proves safe and effective, it will hasten the day gene therapy becomes widely used in clinical practice.``
The Ann Arbor experiment, which received final FDA approval Monday, is medical science`s latest attempt at immunotherapy, a tantalizing but controversial mode of treatment that rarely works, but when it does the results are spectacular.
It is now possible, using genetic engineering, to prepare large amounts of DNA, or genetic material, in the laboratory. At Michigan, this DNA will be coated by harmless fat particles, or liposomes, and injected into a patient`s melanoma tumor. The liposomes allow the genes to slide past the cell`s protective membrane.
Once inside, the DNA has been engineered to produce a protein that invites attack by the soldiers of the body`s immune system. These soldiers are white blood cells called killer T-cells, believed to be responsible for destroying tumors. When HIV-infected people, for instance, lose their T-cells, they become susceptible to a host of cancers.
The purpose of the new treatment is to determine whether it will cause the immune system to attack cancer cells, including those which thus far have eluded detection. Animal studies have shown that once tipped off to the presence of cancer, the immune system will track down and kill other tumor cells that have not been modified by new genes.
Immunotherapy hinges on the belief that throughout life the human immune system vigilantly protects against cancer and in extremely rare circumstances can even reject an erupting tumor as if it were just another germ or transplanted tissue.
Most importantly, immune cells work systemically, ceaselessly patrolling the entire body. That means it might be possible to train them to seek out and destroy cancer cells that have broken off from the original tumor and spread. A surgeon`s knife can cut out solid tumors, but malignant cells that migrate to distant sites to continue their wild division are cancer`s greatest danger. Proponents believe immunotherapy will soon augment the standard treatments of surgery, chemotherapy, and radiation that together cure only about half of those who develop cancer. About 514,000 Americans will die of the disease this year.
A leading immunotherapy strategy has been to devise ways to genetically treat protein molecules called antigens on the surface of cancer cells and turn them into flashing targets for immune defenders to aim for. The Ann Arbor experiment seeks to develop such a cancer vaccine.
But researchers have been stymied by their inability to determine which of the myriad proteins that stud the surface of a tumor cell-so-called tumor antigens-would be most likely to provoke a potent immune response. Most antigens that have been discovered on tumor cells are also found on normal cells.
In November 1991, Belgian researchers reported discovery of the first set of three tumor antigens that arouse the activity of killer T-cells.
Also that month, scientists at Johns Hopkins University used gene therapy to rid mice of an existing cancer by stimulating the animals` own immune system to destroy tumor cells.
Similar animal studies were conducted by Nabel in Ann Arbor. Immunotherapy progress has been slow, he admits, but the first biologic therapies have helped about half the human patients on whom they have been tried, and even cured a few.
Conventional therapies had failed these patients and all had been sent home by their doctors to die.
The incidence of melanoma has risen dramatically in the last 50 years. Although extremely curable when diagnosed and treated early, the so-called black-mole cancer will strike about 32,000 Americans this year, and about 6,700 will die of the disease, many of them in less than a year after the fast-growing cancer starts to spread.
``Our patients are pioneers, and they`re not expecting to be cured by this experiment,`` Nabel said. ``They`re doing it for humanity.
``But I believe their bravery will open a door. It will lead to new treatments for a variety of cancers and other human diseases.``