Monoclonal antibodies for gram-negative sepsis

Article Abstract:

Two monoclonal antibodies for treating gram-negative sepsis are currently being evaluated in clinical trials. These agents are directed against endotoxin, a component of the bacterial cell wall which, when released as a consequence of bacterial degradation, causes a series of physiological events that can lead to death. Sepsis, and its complication, septic shock, is associated with a death rate as high as 70 percent. The monoclonal antibodies discussed in this article are directed against regions of the endotoxin molecule and are manufactured by Centocor and Xoma. HA-1A, the Centocor product, binds to lipid A, the toxic part of the endotoxin molecule. In one clinical trial, 543 patients with sepsis received either a single dose of HA-1A or a small amount of human serum albumin (a placebo treatment). Patients also were treated with antibiotics. Two hundred had gram-negative sepsis, of whom 105 received HA-1A. Mortality among this group was 30 percent, compared with 49 percent in the placebo group (95 patients). Fifty-four patients with gram-negative sepsis had progressed to shock before receiving HA-1A. Thirty-three percent in this group died, compared with 57 percent of those in shock (47 patients) who received the placebo. Complications of sepsis, such as disseminated intravascular coagulation (widespread formation of blood clots), acute kidney or liver failure, and adult respiratory distress syndrome, resolved faster among patients who received the antibody. A trial using E5, made by Xoma, showed similar mortality among patients treated with E5 and those receiving the placebo (40 percent and 41 percent, respectively). For the 316 patients with proven gram-negative sepsis, mortality was 38 percent and 41 percent. These antibodies appear to be safe, but they are expensive. A single dose of HA-1A in Europe costs $3,700. Some patients will benefit from these agents, but the antibodies are costly and selecting the patients to receive them will be difficult. (Consumer Summary produced by Reliance Medical Information, Inc.)

Bacterial infections, Septic shock, Septicemia, Centoxin (Medication)

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Rituximab for non-Hodgkins lymphoma

Article Abstract:

The FDA has approved the use of rituximab for treating low-grade B-cell non-Hodgkin's lymphoma. It is a monoclonal antibody marketed by IDEC Pharmaceutical/Genentech under the brand name Rituxan. There have not been many clinical trials of the drug, but in those which have been done, rituximab, either by itself or in combination with other drugs, can produce a complete response in some patients with low grade B-cell non-Hodgkin's lymphoma with relatively few adverse effects.

Non-Hodgkin's lymphomas, Rituxan (Medication)

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Gemtuzumab for relapsed acute myeloid leukemia

Article Abstract:

The FDA has approved a monoclonal antibody combined with an antibiotic for the treatment of myeloid leukemia. Sold under the trade name Mylotarg, it is an antibody against the CD33 surface antigen, which is expressed on leukemic cells.

Acute leukemia, Promyelocytic, Acute myelocytic leukemia, Mylotarg (Medication)

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