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Hodgkins's Disease

Clinical trials using Yttrium-90 labeled anti-ferritin polyclonal Fab2 has met with some success (62% response rate) in patients with end stage Hodgkin's for whom no other curative treatment is available. These patients also receive autolo-gous bone marrow transplants following treatment (Chapter 17).

Immunodiagnosis

Even if a proposed monoclonal antibody does not reach the high titer/selective toxicity needed for immunotherapy, these molecules can have other value. Monitoring carcinoembryonic antigen (CEA) levels using monoclonal antibodies to CEA, following colon tumor resection, has proven to be a useful means of assessing recurrence, as has following pHCG levels following treatment for choriocarcinoma. Other studies are investigating the use of radiolabeled monoclonal antitumor antibodies (along with a Gamma camera) to detect (by radiography) the localization of tumor deposits in those patients.

Septic shock

There has been interest in the use of anti-tumor necrosis factor (anti-TNF) monoclonal antibodies in the treatment of septic shock. The shock response, with concomitant low blood pressure, increased vascular permeability, pyrexia etc. is believed to be initiated by massive release of TNF by activated macrophages. The "shock" response is a particular problem in instances of gram negative sepsis, where lipopolysaccharide (LPS) released by such organisms has profound TNF inducing capacity, leading to a high morbidity/mortality. Numerous clinical trials of infusion of anti-TNF monoclonal antibodies have been reported in the last several years, though to date none has shown the profound effect hoped for.

Xenotransplantation

Xenotransplantation (transplantation of organs across species) is initially limited by hyperacute rejection responses, attributed to xenoantibodies. These xenoantibodies are naturally occurring antibodies directed to tissue antigens of the donor species. When these antibodies bind to the donor antigens, complement activation occurs which leads to early (minutes/hours) graft thrombosis and graft loss. Strategies to overcome this problem include the use of anti-complement component antibodies, or even artificial antigen-columns for removal of the natural antibodies in recipient serum.

Drug abuse

The interaction of antibody with a drug should neutralize the drug by preventing binding to its receptor. Animal studies using anti-drug Fab2 fragments, instead of intact antibodies, to counteract the effects of an overdose of PCP (angel dust) have reported that behaviors associated with the drug were eliminated in a matter of minutes.

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