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Protinádorová aktivita IL-2 a IL-7 imunokomplexů v kombinaci s αCTLA-4 a αPD-1 monoklonálními protilátkami / Antitumor activity of IL-2 and IL-7 immunocomplexes in combination with αCTLA-4 and αPD-1 mAbs

Biological activity of IL-2 and IL-7 in vivo is significantly increased when complexed with some of the respective anti-cytokine mAb. Different immune cell subsets can be preferentially stimulated depending on the anti-IL-2 mAb used to complex IL-2. IL-2/anti-IL-2 mAb S4B6 immunocomplexes (IL-2/S4B6) induce preferential expansion of CD122high cells whereas IL-2/anti-IL-2 mAb JES6-1 immunocomplexes (IL-2/JES6-1) highly selectively stimulate CD25high cells in mice. Similarly, IL-7/anti-IL-7 mAb M25 immunocomplexes (IL-7/M25) possess higher stimulatory activity for both naïve and memory CD8+ T cells in vivo in comparison to free IL-7. CTLA-4 and PD-1 molecules are inhibitory receptors which negatively regulate proliferation, survival and effector functions of T cells. Blocking antibodies against these molecules represent promising immunotherapeutic tool for treatment of malignant diseases. We examined possible synergism of IL-2/S4B6 and αCTLA-4 plus αPD-1 mAbs in tumor-bearing mice. We found that the expansion of recently activated CD8+ T cells driven by IL-2/S4B6 was further augmented by αCTLA-4 plus αPD-1 mAbs. However, these two immunotherapeutic approaches did not show synergistic antitumor activity in any mouse tumor model tested. Next, we showed that IL-7/M25 possessed higher biological activity...

Identiferoai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:405759
Date January 2019
CreatorsHnízdilová, Tereza
ContributorsKovář, Marek, Hájková, Michaela
Source SetsCzech ETDs
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/masterThesis
Rightsinfo:eu-repo/semantics/restrictedAccess

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