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Immunocomplexes of IL-2 and anti-IL-2 mAbs as a novel class of selective and extremely potent immunostimulators
Tomala, Jakub ; Kovář, Marek (advisor) ; Smetana, Karel (referee) ; Špíšek, Radek (referee)
vi ABSTRACT IL-2 has been used in cancer therapy and also for other applications like treatment of chronic viral infections or as an adjuvant for vaccines. However, treatment with IL-2 is rather difficult due to its severe side effects. These toxicities, associated with high-dose treatment necessary for IL-2 to function, have been found the most limiting factor for IL- 2 applications. Further, particular anti-IL-2 monoclonal antibodies (mAb) can actually increase biological activity of IL-2 rather than block it. Binding of IL-2 to anti-IL-2 mAb creates a superagonistic immunocomplexes which have dramatically higher and selective biological activity in comparison to free IL-2 in vivo. Such approach may finally over- come the difficulties associated with administration of IL-2, thus opening brand new scopes for IL-2 and its application not only in the field of tumor therapy. We have shown that IL-2 immunocomplexes composed of IL-2 and anti-IL-2 mAb S4B6 (IL-2/S4B6) stimulate predominantly cells expressing CD122 and CD132 (dimeric IL-2 receptor), i.e. NK and MP CD8+ T cells, with Treg, T and NKT cells being expanded as well. IL-2/S4B6 are able to drive the expansion of activated naive CD8+ T cells into functional memory-like CD8+ T cells. Moreover, these immunocomplexes exert therapeu- tical potential alone...
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Expanzi aktivovaných CD8+ t-lymfocytů lze výrazně zvýšit podáváním komplexů IL-2 a anit-IL-2protilátky
Tomala, Jakub ; Kovář, Marek ; Strohalm, Jiří ; Etrych, Tomáš ; Ulbrich, Karel ; Říhová, Blanka
By using the model of adoptively transferred transgenic CD8+ cells (OT-I) labeled by CFSE dye, we have measured clonal expansion, proliferation and expression of surface markers after various stimulation.We have studies prophylactic effect of complexes, alone or in combination with other cytokines, on various cancer cell lines in vivo. Our results indicate such approach is very promising and could be potent therapeutical tool in tratment of cancer
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