Alerting immunity, hand in glove.

Alerting immunity, hand in glove 

One of the more elegant methods of immunologic tinkering involves manipulating a molecule with the inelegant name anti-idiotypic antibody. The process, based on principles laid out by Nobel Prize winner Niels K. Jerne, is a way of activating the immune system to attack things it has been ignoring but that don't belong in the body.

Two recent reports detail advances in learning how to use anti-idiotypic antibodies to fight viral diseases and cancer. In one, Wistar Institute researchers in Philadelphia induced mice to produce antibodies to human cancer cells. The second report, from the Southwest Foundation for Biomedical Research in San Antonio, Tex., showed that an anti-idiotypic antibody against hepatities B protected chimps from the disease.

Both experiements relied on Jerne's network hypothesis -- the idea that the immune system is preprogrammed to be activated by idiotypes, portions of antibodies that control their specificity. Idiotypes can provoke anti-idiotypes, which in turn can provoke anti-idiotypes that attach to the initial provoker as well as to the anti-idiotype.

The idiotype recognizes portions of disease organisms or cancer cells that can be thought of as sticking out from those objects like hands. Idiotype-containing "gloves," or antibodies, fit the foreign substance. The researchers in both studies injected these antibodies into animals, which then made second antibodies, or anti-diotypes, that fit into the gloves like the original hands. The second antibodies were then used to induce a third antibody, the anti-anti-idiotype.

Earlier work had hinted at the ability of these third antibodies to fight cancer (SN: 4/6/85, p. 213). Wistar researchers Dorothee Herlyn, Alonzo H. Ross and Hilary Koprowski started with an antibody (the glove) to antigens on human cancer cells (the hand) and injected it into goats. The goats made antibodies to the antibody, and these were used to immunize rabbits and mice. Bot groups of animals produced "glove-shaped" antibodies -- technically, anti-anti-idiotype antibodies -- that bound not only to the goat antibody but also to the original human cancer cells, they report in the April 4 SCIENCE.

The point of using the second antibody, Herlyn told SCIENCE NEWS, is to present the image of the foreign substance in such a way that the body will react to it whereas it didn't react to the initial "hand". In addition, the immunizing antibody is easier to produce than tumor proteins and may also be safer, she says.

The researchers thought of using anti-idiotypes because of a peculiar result in cancer treatment trials at Stanford University in which antibodies against blood cell cancers were used (SN: 8/22/81, p. 117). In some cases, the body began reacting against the cancer long after the injected antibodies were gone. Clinical trials of anti-idiotype vaccines have begun in Europe and are just beginning at Wistar, Herlyn says.

Anti-idiotype vaccines against bacteria and viruses have already proved useful in mouse and rat trials. In the April 11 SCIENCE, Ronald C. Kennedy, Gordon R. Dressman and their colleagues describe successful testing in chimpanzees of an anti-idiotypic vaccine against hepatitis B virus.

They generated their vaccine by injecting rabbits with human antibodies to hepatitis B; the resulting rabbit antibodies were then injected into two chimpanzees, both of which developed immunity. "What this says is that anti-idiotypes do represent a feasible candidate for [preventing] human disease," says Kennedy.

One advantage of anti-idiotypic vaccines is that unlike conventional vaccines they do not contain any viral components that could potentially induce disease. In addition, Kennedy says, studies of anti-idiotype vaccines in mouse and rat systems indicate they may be able to provoke immunity in newborns, something many conventional vaccines can't do. Kennedy's group is also looking at possible anti-idiotypic vaccines against AIDS.