Phase I study of subcutaneously administered interleukin-2 in combination with interferon alfa-2a in patients with advanced cancer.

Abstract

IL-2 and IFN alpha-2a can be given with tolerable toxicities on an outpatient basis and shows significant activity in patients with metastatic RCC.

Natural killer cell cytotoxicity is enhanced by very low doses of rIL-2 and rIFN-α in patients with renal cell carcinoma

“…Only a few studies have monitored NK cell cytotoxicity during immunotherapy in vivo, all of which only included patients with metastatic RCC [20][21][22][23][24]. They all showed a significant increase in NK cell cytotoxicity, except for one study in which the doses of rIL2 and rIFN-a were lower than those used in the present study [24]; only one study used rIL2 doses similar to those proposed by Buzio et al, but they were not combined with IFNa.…”

Combined Subcutaneous Recombinant α–Interferon and Interleukin–2 in Metastatic Renal Cell Cancer: Results of the Multicentre All Ireland Immunotherapy Study Group

“…Other studies using subcutaneous r–IL2 regimens report treatment discontinuity as a result of toxicity in 10% [14], 12.5% [15]and 18% [16]of patients.…”

Immunotherapy with Interleukin-2: A Study Based on Mathematical Modeling

“…It is also stimulated by IL-2 that is produced by effector cells in an autocrine and paracrine manner (the term p 1 xz/(g 1 + z), p 1 is the rate at which the effector cells grows and g 1 is the half saturation constant). A clinical trial shows that there are immune stimulation effects from treatment with IL-2 (Keilholz et al, 1994;Gause et al, 1996;Hara et al, 1996;Kaempfer et al, 1996;Curti et al, 1996), and there is a time lag between the production of interleukin-2 by activated T-cells and the effector cell stimulation from treatment with IL-2. Hence, a discrete time delay is being added to the second term of the first equation of the system (1), which modifies to…”

“…Developing schemes for immunotherapy or its combination with other therapy methods are the major attempts at present, which aim at reducing the tumor mass, heightening tumor immunogenicity and removing the immunosuppression induced in an organism in the process of tumor growth. Recent progress in this line has been achieved through immunotherapy, which refers to the use of cytokines (protein hormones that mediate both natural and specific immunity) usually together with adoptive cellular immunotherapy (ACI) (Rosenberg and Lotze, 1986;Schwartzentruber, 1993;Rosenberg et al, 1994;Keilholz et al, 1994;Gause et al, 1996;Hara et al, 1996;Kaempfer et al, 1996;Curti et al, 1996;Rabinowich et al, 1996).…”