Journal
ONCOIMMUNOLOGY
Volume 11, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2022.2028961
Keywords
Cancer immunotherapy; costimulation; tumor necrosis factor superfamily members; T-cells; Fc fusion protein
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Targeting costimulatory receptors of the TNFSF to activate T-cells and promote anti-tumor T-cell function has potential in cancer immunotherapy. Dual-acting costimulatory molecules, formed by combining different members of the TNFSF, can activate two different receptors on cells. Incorporating TNF superfamily costimulatory ligands into a dual-acting molecule enhances T-cell proliferation and anti-tumor activity.
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.
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