Fc-based Duokines: dual-acting costimulatory molecules comprising TNFSF ligands in the single-chain format fused to a heterodimerizing Fc (scDk-Fc).

Abstract

Targeting costimulatory receptors of the tumor necrosis factor superfamily (TNFSF) to activate T-cells and promote anti-tumor T-cell function have emerged as a promising strategy in cancer immunotherapy. Previous studies have shown that combining two different members of the TNFSF resulted in dual-acting costimulatory molecules with the ability to activate two different receptors either on the same cell or on different cell types. To achieve prolonged plasma half-life and extended drug disposition, we have developed novel dual-acting molecules by fusing single-chain ligands of the TNFSF to heterodimerizing Fc chains (scDuokine-Fc, scDk-Fc). Incorporating costimulatory ligands of the TNF superfamily into a scDk-Fc molecule resulted in enhanced T-cell proliferation translating in an increased anti-tumor activity in combination with a primary T-cell-activating bispecific antibody. Our data show that the scDk-Fc molecules are potent immune-stimulatory molecules that are able to enhance T-cell mediated anti-tumor responses.

• Authors: Nadine Aschmoneit, Katharina Kocher, Martin Siegemund, Martina S Lutz, Lennart Kühl, Oliver Seifert, Roland E Kontermann
• Journal: Oncoimmunology (Oncoimmunology) Vol. 11 Issue 1 Pg. 2028961 ( 2022) ISSN: 2162-402X [Electronic] United States
• PMID: 35083097 (Publication Type: Journal Article)
• Copyright: © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Chemical References

• Antibodies, Bispecific
• Ligands
• Tumor Necrosis Factor-alpha

Topics

• Antibodies, Bispecific (therapeutic use)
• Humans
• Immunotherapy (methods)
• Ligands
• Neoplasms (drug therapy)
• Tumor Necrosis Factor-alpha (therapeutic use)