Drug gives new transplant hopes

Press, 1 October 1979, Page 18

Drug gives new transplant hopes

From the “Economist”

Organ transplants are at best a desperate gamble. The operations can be tricky. Worse, the body’s own natural defences against “foreign” intruders of all kinds (bacteria, fungi, viruses) then normally attack the newly grafted tissue. The drugs typically used to combat this are only partially effective, can have unpleasant (and even dangerous) side effects, and tend to suppress patients’ immunity to ordinary infection.

A trick to disarm man’s immune system selectively — against tissue grafts

alone — has eluded researchers to date.

Happily, papers detailing very recent research on transplants (presented this month at the British Association for the Advancement of Science) hold out hope on all three fronts.

Safer operating procedures for liver transplants have been developed by doctors at the University department of surgery in Cambridge. England, in collaboration with King’s College Hospital in London. The team is also testing plinically a new postoperative drug to suppress patients’ rejection of kidney grafts.

Called Cyclosporin A and developed by Switzerland’s Sandoz, the new drug promises to be very effective — not least because it spares patients the horrid side effects of steroids. These include a puffy “moon” face, stunted growth or even a crippling collapse of joints. The most exciting recent developments are the results of laboratory experiments on rats being conducted by a team at the Royal Postgraduate Medical School of London’s Hammersmith Hospital. These suggest that it may be possible to persuade the body not to fight a tissue transplant in the first place.

That would do away with the need for immunosuppressive drug therapies altogether and give patients a chance of retaining a useful new organ not merely for months or a few years but for a normal lifetime.

To date, liver transplant surgeons, for example, congratulate themselves if half their patients survive for at least a year. Only one has lived as long as eight years. Classical immune theory rests on two fundamental assumptions:

® Antigens trigger the immune response. Antigens are the distinctive molecular structures on the surface of

cells which identify them as either “self” or “foreign.” Except with identical twins, different people as a rule have different “self” antigens, and recognise those of others as foreign. Therefore the foreign (or “transplant”) antigens introduced by a graft induce the body to reject the graft. • The immune system dis-

plays “memory.” Prime it by exposing it to any particular foreign antigen once, and it will act against a second exposure faster and more effectively. That, after all, is why vaccines work. However, it now appears that this characterisation of the immune response is too simple. The research on rats has produced surprises.

If a rat about to receive a kidney transplant from an unrelated donor is first injected with tissue cells (or even antibodies) from that donor, the rat may not reject the “foreign” graft. On the contrary, it looks as if this procedure can prolong the survival of the transplant indefinitely. Most of the injected rats do begin to display an attack on the transplants shortly after the operation. But instead of continuing inexorably to the destruction of the graft, the attack ceases before major damage has been done. The rats then improve progressively. Indeed, they also become less and less responsive to the transplant antigens of the original donor rats: experiments have shown they can accept further transplants (even of entire hind limbs) from the same donors without problems. But why does this happen? Experiments at Hammersmith have confirmed that the kidneys used in the transplants display a normal number of transplant antigens. If these do not trigger an ordinary immune response, could it be that they selectively disarm the immune system instead — inducing the body to accept further grafts? In order to test this un-

orthodox proposition the researchers in recent weeks transplanted some of the kidneys a second time. Kidneys originally taken from one strain of rats (call it A) and successfully transplanted into a second strain (B> were grafted into still other Bstrain rats.

These rats had normal immune systems: unlike their fellows, they had not been previously injected with Astrain antigens (nor, of course, had they been treated with drugs). Even so, they too accepted the transplants. The implication is that the mere physical presence of transplant antigens is not, in itself, sufficient to trigger a normal immune response. It may be that in order to do so the antigens must be introduced on particular types of cells. Perhaps only certain lymphoid and blood cells can trigger a full response and not the cells of the grafted tissue itself. If so, a better understanding of the mechanisms involved could lead to better transplant procedures for peo. '< But these are early days for such experiments. The new technique is not yet foolproof — even on rats. Occasionally, an injected rat has displayed a classic immune response — rejecting its transplant with exceptional vigour.