| Autor: |
Casadesús, Ana Victoria, Deligne, Claire, Diallo, Béré Kadjdiatou, Sosa, Katya, Josseaume, Nathalie, Mesa, Circe, León, Kalet, Hernández, Tays, Teillaud, Jean-Luc |
| Předmět: |
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| Zdroj: |
OncoImmunology; 2020, Vol. 9 Issue 1, p1-11, 11p |
| Abstrakt: |
Anti-CD20 treatment represents a therapeutic benefit for patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing patients. Among them, the combination of anti-CD20 and IL-2 that induces T cell response has been hampered by the expansion of FoxP3+ Tregs that strongly express the high affinity IL-2 receptor (IL-2R αβγ). We explore here the anti-tumor effect of an anti-CD20 antibody combined with a mutated IL-2 (no-alpha mutein) which has a disrupted affinity for the IL-2R αβγ. We demonstrate that anti-CD20/no-alpha mutein combination significantly augments the survival rate of mice challenged with huCD20+ cells as compared to animals treated with anti-CD20 ± IL-2. Moreover, the combination with no-alpha mutein but not IL-2 provokes an increase of granzyme B and perforin in splenic NK and CD8+ T cells, a reduction of Tregs and an increase in activated macrophages. The former combination also induces a T helper profile different from that obtained with IL-2, with an earlier polarization to Th1 and no increase in Th17. The therapeutic effect of anti-CD20/no-alpha mutein was accompanied by an expansion of peripheral central (TCM) and effector (TEM) memory CD8+ T cell compartments. Last, as opposed to IL-2, no-alpha mutein administered at the beginning of anti-CD20 treatment did not dampen the long-term protection of surviving mice after tumor rechallenge. Thus, this study shows that the combination of anti-tumor antibodies and no-alpha mutein is a promising approach to improve the therapeutic effect of these antibodies by potentiating NK/macrophage-mediated innate immunity and the adaptive T-cell response. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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