Therapeutic monoclonal antibody okayed.

Therapeutic monoclonal antibody okayed

The Food and Drug Administration (FDA) has approved a monoclonal antibody for use in acute rejection episodes following kidney transplants. Though monoclonal antibodies are already used on blood and tissue for diagnostic purposes, last week's announcement marked the first time such an antibody has been okayed for use in humans. In making the announcement, FDA Commossioner Frank E. Young said he expects more monoclonal antibodies will be approved following controlled clinical trials.

The tricky thing about kidney transplants these days is ot the operation itself but the recipient's attempt to reject the organ, even when a close relative is the donor. Rejection comes in three phases -- the hyperacute stage immediately following the transplant, the acute stage days or weeks later, and the chronic stage, which lasts as long as the transplanted organ. All are presently prevented or controlled with drugs, which are not always effective.

The newly approved monoclonal antibody, caled OKT3, attacks T cells, a subset of which can cause acute rejection of the kidney. In a previously reported human trial, OKT3 reversed acute rejections in 58 of 62 transplant recipients, or 94 percent. Conventional drug treatment with steroids or cyclosporine was able to reverse rejection in only 45 of 60, or 75 percent, with failure commonly resulting in the loss of the kidney.

OKT3 is given as a one-shot injection when an acute rejection occurs; within hours, the T cells burst and the episode halts. While the kidney is protected, there can be some side effects, including fevers, chills, tremors, shortness of breath, chest pain and nausea.

The FDA approval applies to use of the antibody in an initial acute rejection. Whether it will prove valuable for subsequent attacks, or whether the body's immune system will disable the foreign antibody, remains to be seen.

Monoclonal antibodies are made by hybridomas, which are hybrids of antibody-producing cells and long-lived tumor cells. To make a hybridoma, researchers immunize an animal, in this case a mouse, with a specific substance, in ths case human T cells. The mouse's antibody-producing spleen cells are collected and fused to tumor cells. Each resulting hybrid is cloned, and the clonal line that produces the desired antibody is selected and put into a production line.

Hybridomas are already used for producing uniform antibodies needed in diagnostic testing kits. And several human trials are under way to test the ability of monoclonal antibodies to combat cancer and immune system diseases.

About 7,000 kidney transplants are done each year in the United States, and about 60 percent of them result in acute rejection. But the OKT3 work is expected to have implications beyond this group. "The theory of using a [mouse] monoclonal antibody in a man is now established," says Thomas Zuck of the FDA. "The safety issues are behind us."