Clinical and immunological evaluation of 20 patients with advanced colorectal cancer treated with high dose recombinant leukocyte interferon-alpha A (rIFN alpha A).

A total of 20 patients with advanced colorectal cancer received recombinant leukocyte interferon-alpha A (rIFN alpha A) either chronically (group I: twice a week up to 20 X 10(6) IU/m2 i.m.) or cyclically (group II: 1-4 periods of 8 consecutive days up to 20 X 10(6) IU/m2 i.m. daily at 20-days intervals) over a period of 12 weeks. There was 1 partial response, 1 mixed response and 1 patient with stable disease, whilst 17 patients had progressive disease. Median survival was 15.5 months. Survival was significantly shorter when the extent of hepatic disease was greater than 25% (P = 0.05), extrahepatic disease was extensive (P less than 0.005), alkaline phosphatase level was greater than 2 X normal (P less than 0.02), or performance status was less than 100% (P less than 0.001). Toxicity consisting mainly of fever, fatigue, anorexia and weight loss was serious in group I and minimal in group II. Administration of rIFN alpha A led to a "short lived" augmentation of natural killer (NK) cell activity. In the cyclically treated group this was a recurrent phenomenon whereas a marked lasting depression of NK cell activity was seen in chronically treated patients. Interferon-gamma production capacity was significantly stimulated during rIFN alpha A therapy. The differences in toxicity and immunostimulatory effects between the two schedules may be of importance in the design of further studies.

Effects of treatment with azathioprine and cyclosporin A on interferon-gamma production by peripheral blood leukocytes of renal allograft recipients.

We have studied the concanavalin A (ConA)-induced interferon gamma (IFN-gamma) production of peripheral blood mononuclear cells (PBMC) of renal allograft recipients. Both under immunosuppressive treatment with azathioprine and with cyclosporin A (CsA) the PBMC of these patients proved deficient for IFN-gamma production when compared to those of healthy controls. After conversion from conventional azathioprine to CsA medication the ConA-induced IFN-gamma production increased.

Mitogenic responses of canine peripheral blood lymphocytes to staphylococcal protein A.

In order to produce long term lymphoid cell cultures from canine lymphocytes of known histocompatibility antigen specificities, mitogenic responses to staphylococcal protein A (SpA) were examined and compared with those of phytohaemagglutinin (PHA) and concanavalin A (Con A). SpA was found to be the strongest mitogen tested with significant responses to concentrations as low as 31 ng/ml. There was a decrease in responsiveness above optimal mitogen concentrations with SpA and PHA. Peak responses were observed at lower concentrations for longer incubation times. PHA showed a rapid fall off in thymidine uptake below optimal concentrations whereas the SpA dose-response curve was less steep and a shoulder or secondary peak of activity was observed at low SpA concentrations in some cases. Continuous SpA stimulation of lymphocyte cultures resulted in an initial period of cell proliferation followed usually by a second period of cell proliferation around week 7 of culture. To date, viable cell cultures have been maintained for up to 12 weeks in vitro. SpA lymphoblast cultures behave normally in microcytotoxicity tests for serologically defined DLA histocompatibility antigens and remain functional in natural killer (NK) and PHA induced cell mediated cytotoxic reactions against 51Cr-labelled tumour target cells but were not themselves susceptible as target cells for NK activity.