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At least 217 records · Page 12Linked to original sources

Immunological monitoring of clinical trials using biological response modifiers.

Phase I clinical trials of Biological Response Modifiers must be designed to provide information not only regarding toxicities, pharmacokinetics and anti-tumor response, but also on their many immunomodulatory properties. If BRMs are to be used rationally, then detailed standardized data must be obtained in such a way as to enable meaningful conclusions to be drawn from the monitoring assays. Assay selection, timing for monitoring and methods for data interpretation are important considerations in the design of such trials.

Clinical Trials as Topic↗

Monoclonal antibodies to human T cell subsets: use for immunological monitoring and immunosuppression in renal transplantation.

Sequential monitoring of peripheral blood T cell populations was performed in normal control individuals and in 55 renal allograft recipients. In addition, 66 patients exhibiting prolonged renal allograft survival were each evaluated at least once with the same monoclonal antibodies. A normal or elevated OKT4:OKT8 ratio, especially in the presence of rising numbers of OKT4+ cells was predictive of possible future graft rejection. This observation, when followed by rising serum creatinine values coupled with biopsy evidence of glomerulopathy, was found in at least 15% of graft recipients. In a small number of patients, graft rejection episodes were successfully suppressed by administration of therapeutic doses of OKT3 antibody. However, production of anti-OKT3 antibodies was observed and may be expected to limit administration of this agent to a single short course in each patient.

Acute Disease↗

Immunological monitoring of viral infections in renal transplant recipients.

Twelve viral episodes occurred in 54 antilymphocyte globulin-treated renal transplant recipients (two primary cytomegalovirus, seven cytomegalovirus reactivations, one chickenpox, two influenza). In 11 of 12 cases the ratio between peripheral T4 and T8 subsets fell (from 1.698 to 0.986, p less than 0.01) due both to a reduction of T4+ and to an increase of T8+ cells. T10+ and 5/9 subsets also increased. Suppressor T-cell function, as measured by two simultaneous assays, was enhanced. In antibody-negative CMV patients the reversal of T4/T8 ratio preceded the appearance of specific IgM. T4/T8 ratios rapidly returned to normal in mild episodes, but remained reverted in symptomatic CMV patients for several months, despite a reduction in the immunosuppressive regimen. Symptomatic viral episodes displayed marked imbalances in T cell subset numbers and function, while in asymptomatic cases the changes were less evident.

Chickenpox↗