Potent antitumour activity of interleukin-2-Fc fusion proteins requires Fc-mediated depletion of regulatory T-cells.

ABSTRACT: Interleukin-2 (IL-2) is an established therapeutic agent used for cancer immunotherapy. Since treatment efficacy is mediated by CD8⁺ and NK cell activity at the tumour site, considerable efforts have focused on generating variants that expand these subsets systemically, as exemplified by IL-2/antibody complexes and 'superkines'. Here we describe a novel determinant of antitumour activity using fusion proteins consisting of IL-2 and the antibody fragment crystallizable (Fc) region. Generation of long-lived IL-2-Fc variants in which CD25 binding is abolished through mutation effectively prevents unwanted activation of CD25⁺ regulatory T-cells (Tregs) and results in strong expansion of CD25^- cytotoxic subsets. Surprisingly, however, such variants are less effe

SUBMITTER: Vazquez-Lombardi R 

PROVIDER: S-EPMC5437307 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature