Antitumor activity of IL-2/anti-IL-2 mAb immunocomplexes exerts synergism with that of N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugate due to its low immunosuppressive activity

0367735 - MBÚ 2012 RIV DE eng J - Článek v odborném periodiku
Tomala, Jakub - Chmelová, Helena - Strohalm, Jiří - Ulbrich, Karel - Šírová, Milada - Říhová, Blanka - Kovář, Marek
Antitumor activity of IL-2/anti-IL-2 mAb immunocomplexes exerts synergism with that of N-(2-hydroxypropyl)methacrylamide copolymer-bound doxorubicin conjugate due to its low immunosuppressive activity.
International Journal of Cancer. Roč. 129, č. 8 (2011), s. 2002-2012. ISSN 0020-7136. E-ISSN 1097-0215
Grant CEP: GA AV ČR IAA500200712; GA ČR GD310/08/H077; GA ČR GP301/07/P192; GA MŠMT 1M0505
Výzkumný záměr: CEZ:AV0Z50200510; CEZ:AV0Z40500505
Klíčová slova: IL-2 immunocomplexes * NK cells * HPMA copolymer-bound doxorubicin
Kód oboru RIV: EC - Imunologie
Impakt faktor: 5.444, rok: 2011

Interleukin (IL)-2 has been approved for treatment of metastatic renal cancer and malignant melanoma. However, its unfavorable pharmacologic properties, severe side effects and the negative role of IL-2 in maintaining T regulatory cells are severe drawbacks. It has been shown that immunocomplexes of IL-2 and certain anti-IL-2 mAbs possess selective and high stimulatory activity in vivo. Here, we show that IL-2/S4B6 mAb immunocomplexes expand not only CD122high subsets and newly activated CD81 T cells but also natural killer T cells and cd T cells. Further, we demonstrate that natural killer (NK) cells expanded by IL-2/S4B6 mAb immunocomplexes in vivo have high cytolytic activity, which can be further increased by coadministration of IL-12. We also demonstrate that IL-2/S4B6 mAb immunocomplexes possess noticeable antitumor activity in two syngeneic mouse tumor models, namely BCL1 leukemia and B16F10 melanoma, but only if administered early in tumor progression
Trvalý link: http://hdl.handle.net/11104/0202300