Trifunctional antibody-cytokine fusion protein formats for tumor-targeted combination of IL-15 with IL-7 or IL-21.

ABSTRACT: Cytokines from the common gamma chain receptor family, such as IL-15, IL-21 and IL-7, show promise for cancer immunotherapy and have been incorporated individually into the immunocytokine approach. However, their efficacy as monotherapy is limited. Here, we investigated the molecular design of tumor-directed trifunctional antibody-cytokine fusion proteins for a combinatorial approach of IL-15 with either IL-7 or IL-21. Various fusion proteins differing in antibody format, cytokine composition and arrangement were generated and cooperative cytokine activity assessed in solution and bound to target cells. Comparative analysis revealed that formats with cytokines positioned at the N- and C-termini of the antibody were more effective than those arranged in series. For the former design, cooper

SUBMITTER: Moller AM 

PROVIDER: S-EPMC12075275 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature