In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2.

Abstract

Purified recombinant human interleukin 2 (RIL 2) derived from E. coli containing the inserted gene encoding for IL 2 was administered to 20 patients with a variety of malignancies. Toxicity was dose related and included fever, chills, malaise, arthralgias, myalgias, and unexpectedly, weight gain related to marked fluid retention. All patients receiving more than 10(5) U/kg total cumulative dose developed evidence of fluid retention, and all patients requiring discontinuance of RIL 2 (11/20) received total doses of between 2.54 X 10(5) U/kg to 15.4 X 10(5) U/kg. The limiting dose with this preparation was 3000 U/kg/hr by continuous administration or 10(6) U/kg by bolus administration. IL 2 was rapidly cleared from the plasma, with a half life of 6.9 min, and a later delayed clearance was consistent with a two-compartment model, with slower release from the extravascular space back into the plasma compartment. A marked change in lymphoid cells in the periphery was noted with an early depletion of all lymphoid cells, followed by an expansion of such cells with continuous IL 2 administration. A twofold to 16-fold expansion of total lymphoid cells in the peripheral blood could be demonstrated. TAC+ cells representing up to 25% of the circulating peripheral blood mononuclear cells could be demonstrated with 3 wk of continuous RIL 2 administration. Interferon-gamma levels increased in patients treated with IL 2. Precursors of lymphokine-activated killer cells generated under standard conditions were depleted within 2 to 3 min after IL 2 administration, but repopulated the peripheral blood after 7 to 10 days of continuous IL 2 administration. No tumor regression was seen in any of the cancer patients treated with IL 2 alone.

Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results

“…[17][18][19] Furthermore, the observed lymphopenia and subsequent lymphocytosis are consistent with the known characteristics of IL-2 and BEMPEG. 14,15,[17][18][19][20][21] Although the dose of BEMPEG chosen for PIVOT IO 001 did not show single-agent antitumor activity, it was well-tolerated and associated with immune response in previous phase I and phase II studies. 14 Additional biomarker analyses are ongoing to further elucidate any potential mechanisms underlying the lack of added efficacy for BEMPEG plus NIVO versus NIVO monotherapy.…”

Bioempowerment of Therapeutic Living Cells by Single‐Cell Surface Engineering

“…Single‐cell surface engineering provides researchers with a toolbox for manipulating individual target cells without the potential danger of disrupting the whole‐body system or metabolism and behavior of bystander cells ( Figure a). [ 160,161 ]…”

“…Singlecell surface engineering provides researchers with a toolbox for manipulating individual target cells without the potential danger of disrupting the whole-body system or metabolism and behavior of bystander cells (Figure 8a). [160,161] Drug-loaded lipid NPs have been conjugated to the surface of T cells, to stimulate the cells in a pseudo-autocrine manner. [37] The conjugation was achieved by the TMMA reaction between the cell-surface thiols and maleimide-bearing lipid NPs.…”

The T-Cell Growth Factor Interleukin-2, Which Is Occasionally Targeted by Autoantibodies, Qualifies as Drug for the Treatment of Allergy, Autoimmunity, and Cancer: Collegium Internationale Allergologicum (CIA) Update 2024

“…Of note, such mAbs would not only change the receptor specificity of endogenously or exogenously applied IL-2 but may also significantly prolong the half-life of the otherwise short-lived IL-2 (T 1/2 only 6-7 min) [42,43] with renal elimination accounting for 75% of IL-2 clearance [44]. The first experimental studies to show such immunomodulatory capacities of injected anti-IL-2 mAbs were conducted by Jonathan Sprent and coworkers [41], and later on by Fred Finkelman and coworkers [43] The Multiple Functions of Interleukin-2 Int Arch Allergy Immunol 2024;185:286-300 DOI: 10.1159/000533677 who demonstrated that murine Treg cells can be selectively expanded by IL-2 complexes (IL-2C) formed upon injection of the rat anti-mouse IL-2 monoclonal antibody JES-6.1A12 (Table 2; Fig.…”