Potentiating effect of IL-2 no-alpha mutein on the antitumoral activity of anti- CD20 therapy
Keywords:
anti-CD20, IL-2 mutein, immunocytokine, immunotherapy, lymphomaAbstract
Introduction: The anti-CD20 antibody rituximab has substantially improved outcomes of patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing lymphomas. The combination of rituximab and IL-2 and the use of immunocytokines based on anti-CD20 antibodies and IL-2 had a limited impact in the clinic due to the toxicity profile associated with IL-2 and the expansion of Treg cells.
Objective: To demonstrate the potentiation of the anti-tumor effect of rituximab -based anti-CD20 antibodies by combining or fusing with IL-2 no-alpha mutein.
Methods: We explore 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 and immunocytokines based on rituximab and this mutein in an EL4-huCD20/C57Bl/6 model and evaluated immune cell populations by Flow Cytometer.
Results: We demonstrate that the antitumor effect of an anti-CD20 antibody was enhanced in combination with the no-alpha mutein. This effect was associated with an increase in the lytic potential of NK and CD8+ T cells, a reduction of Tregs, and was characterized by an earlier polarization to Th1.The fusion, for the first time, of no-alpha mutein to a human IgG1 version of rituximab with functional Fc generated a tri-functional molecule that maintained the recognition of the CD20 antigen, the signaling capacity and in vivo immunomodulation of the cytokine, and improved the in vitro effector functions of this antibody: apoptosis and ADCC, resulting in an in vivo antitumor effect superior to that obtained with low-dose rituximab.
Conclusions: Taken together, our findings suggest that IL-2 mutein is a promising molecule that either combined or fused to antibodies can potentiate anti-CD20 therapy.
Downloads
Published
How to Cite
Issue
Section
License
The journal Anales de la Academia de Ciencias de Cuba protects copyright, and operates with a Creative Commons License 4.0 (Creative Commons Attribution-NonCommercial License 4.0). By publishing in it, authors allow themselves to copy, reproduce, distribute, publicly communicate their work and generate derivative works, as long as the original author is cited and acknowledged. They do not allow, however, the use of the original work for commercial or lucrative purposes.
The authors authorize the publication of their writings, retaining the authorship rights, and assigning and transferring to the magazine all the rights protected by the intellectual property laws that govern in Cuba, which imply editing to disseminate the work.
Authors may establish additional agreements for the non-exclusive distribution of the version of the work published in the journal (for example, placing it in an institutional repository or publishing it in a book), with recognition of having been first published in this journal.
To learn more, see https://creativecommons.org
