About: Depletion of T regulatory cells without need of anti-CD25 mAb for effective chemoimmunotherapy by HPMA-based polymeric drugs and IL-2 immunocomplexes     Goto   Sponge   NotDistinct   Permalink

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  • T regulatory cells (Treg) are key players in inhibiting T cell mediating immune responses. It was shown in numerous tumor models that depletion of Treg cells can restore the capacity of immune system to eliminate tumor cells. Treg cells are depleted most often by anti-CD25 mAb, reflecting their dependency on IL-2 signal. However, anti-CD25 mAb can also eliminate subsequently activated T cells, including those with tumor-specific activity, as antibodies remain relatively long in circulation. Here we suggest first to activate Treg cells by IL-2/JES6-1 mAb immunocomplexes, which possess high stimulatory activity selectively for CD25high cells in vivo, and then deplete them by cell cycle-specific drugs (cytosinarabinoside, hydroxyurea or metothrexate). Such depletion of Treg cells will be used for augmenting the chemoimmunotherapy with new generation of dendrimeric HPMA-based polymeric drugs in combination with IL-2/S4B6 mAb immunocomplexes, which are highly stimulatory for CD122high cells, i.e. memory CD8+ T cells and NK cells and also for recently activated CD8+ T cells. (en)
  • Rozhodující roli v inhibici T buněčné imunitní odpovědi hrají T regulační (Treg) buňky. V mnoha nádorových modelech bylo prokázáno, že deplece Treg buňek může vést k eliminaci nádorových buněk imunitním systémem. Treg buňky jsou nejčastěji depletovány pomocí anti-CD25 monoklonální protilátky (mAb), což obráží jejich závislost na IL-2 signálu. Bohužel, anti-CD25 mAb může taktéž eliminovat následně aktivované T buňky, a to včetně nádor-specifických, protože mAb zůstává relativně dlouho v cirkulaci. Proto navrhujeme nejdříve aktivovat Treg buňky IL-/JES6-1 mAb imunokomplexy, které mají vysokou stimulační aktivitu pro CD25high buňky in vivo, a poté je depletovat pomocí fázově specifických cytostatik (cytosinarabinosid, hydroxyurea, metotrexát). Deplece Treg buněk bude použita pro potenciaci chemoimunoterapie pomocí nové generace polymerních léčiv na bázi HPMA s dendrimerní strukturou v kombinaci s IL-2/S4B6 mAb imunokomplexy, které mají vysokou stimulační aktivitu pro CD122high buňky, t.j. paměťové CD8+ T buňky a NK buňky, a také pro recentně aktivované CD8+ T buňky.
Title
  • Depletion of T regulatory cells without need of anti-CD25 mAb for effective chemoimmunotherapy by HPMA-based polymeric drugs and IL-2 immunocomplexes (en)
  • Deplece T regulačních buněk bez použití anti-CD25 monoklonální protilátky pro potenciaci chemoimunoterapie polymerními léčivy a IL-2 imunokomplexy
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  • GAP301/11/0325
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  • T regulatory cells HPMA-based polymeric drugs IL-2 immunocomplexes chemoimmunotherapy (en)
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