Differential quantitative effects of interleukin (IL)-2 and IL-15 on cytotoxic activity and proliferation by lymphocytes from patients receiving in vivo IL-2 therapy. Clin Cancer Res 1998 May;4(5):1287-96
Date
06/02/1998Pubmed ID
9607589Scopus ID
2-s2.0-0031925166 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
Lymphocytes from patients receiving in vivo interleukin (IL)-2 therapy possess enhanced in vitro proliferative and cytotoxic responses to IL-2. The cells from these patients that respond to exogenous IL-2 are CD56+ natural killer cells expressing intermediate-affinity IL-2 receptor betagamma(c) complexes. Because IL-15 activates cells via these same betagamma(c) receptors, we hypothesized that IL-15 would also activate lymphocytes from patients treated with in vivo IL-2 therapy and therefore that IL-15 might potentially be useful as an immunotherapeutic agent alone or in combination with IL-2. We report here that peripheral blood mononuclear cells (PBMCs) from patients receiving in vivo IL-2 therapy do proliferate in response to IL-15. However, a greater dose of IL-15 is needed to reach the same level of proliferation stimulated by IL-2. The EC50 for IL-2 is 0.21 +/- 0.04 nM (mean +/- SE; n = 18), whereas the EC50 for IL-15-stimulated proliferation is 1.16 +/- 0.16 nM (n = 18). In contrast to the proliferative response, equivalent doses of IL-2 and IL-15 stimulate patient PBMCs to mediate similar levels of cytotoxicity against Daudi, K562, and LA-N-5 tumor targets. Notably, low concentrations of IL-15 that do not stimulate a substantial proliferative response (e.g., 1.0 ng/ml) do boost PBMCs to mediate cytotoxicity against these tumor targets. These distinct dose-response curves for proliferation compared to cytotoxicity suggest that IL-15 should be evaluated for its potential as an immunotherapeutic agent to treat cancer, particularly in regimens providing doses that might minimize the proliferative response (associated with cytokine release and toxic side effects) while maintaining the cytolytic antitumor response.
Author List
de Jong JL, Farner NL, Javorsky BR, Lindstrom MJ, Hank JA, Sondel PMAuthor
Bradley R. Javorsky MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Antigens, CDAntigens, Differentiation, T-Lymphocyte
CD56 Antigen
Cell Division
Dose-Response Relationship, Drug
Humans
Interleukin-15
Interleukin-2
Killer Cells, Natural
Lectins, C-Type
Leukocytes, Mononuclear
Lymphocyte Subsets
Melanoma
Tumor Cells, Cultured