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The in vitro incubation of phytohemagglutinin (PHA)- or alloantigen-stimulated peripheral blood T cells with prothymosin alpha (ProT alpha) resulted in a marked and reproducible increase in the production of interleukin-2 (IL-2). Incubation of T cells with ProT alpha, in the absence of PHA or alloantigen, failed to induce any production of IL-2. ProT alpha by itself did not exert any IL-2 activity. Finally, ProT alpha was shown to increase the expression of IL-2 receptors on phytohemagglutinin- or alloantigen-activated T cells. These data provide the basis for understanding the in vitro immunoenhancing effects of ProT alpha in cellular immune systems.

PURPOSE To evaluate the response rate and the immunorestorative properties of subcutaneously administered interferon alfa-2b (IFN-A2b) in patients with advanced renal cell carcinoma (RCC) and to correlate the immune status with the clinical responses. PATIENTS AND METHODS Twenty-six patients with advanced RCC were treated with recombinant IFN-A2b. The dose was increased progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week, and thereafter to 15 x 10(6) IU subcutaneously. RESULTS Four patients (15%) achieved partial responses (PRs), and five patients (19%) had stable disease (S), whereas 17 patients (65%) progressed. In all patients, blood was withdrawn before IFN treatment and monthly thereafter. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (autoMLR) and allogeneic mixed lymphocyte reaction (alloMLR), interleukin-2 (IL-2) production, expression of IL-2 receptors during the alloMLR, and the production of interleukin-1 (IL-1) by peripheral-blood monocytes. Twelve patients were assessable, four patients had a PR, one patient had S, and seven patients had progressive disease. Striking increases were demonstrated in all parameters 1 month after treatment with IFN-A2b in the four patients who responded and the patient with S. Namely, the autoMLR responses showed a mean increase of 250%, the IL-2 production 247%, the expression of IL-2-specific receptors 446%, the alloMLR responses 160%, and the production of IL-1 262%. On the contrary, the nonresponders did not show any change in their overall immune status, and in some, deterioration of the already depressed immunologic functions was observed. CONCLUSIONS Administration of IFN-A2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC who respond to the treatment. This may have prognostic significance, and certainly more patients are required to be studied for definite conclusions.

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