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FIST, a sword and shield fusokine for cancer immunotherapy.

Penafuerte C, Galipeau J - Oncoimmunology (2012)

Bottom Line: FIST).FIST possesses intriguing gain-of-function properties and induces potent activation of IL2-receptor expressing cells and inhibits tumor-derived angiogenesis.Thus FIST constitutes a first-in-class biological that couples anti-angiogenesis to an immune antitumor response.

View Article: PubMed Central - PubMed

Affiliation: The Rosalind & Morris Goodman Cancer Research Centre; McGill University; Montreal, QC Canada.

ABSTRACT
To antagonize tumor-derived TGFβ contemporaneously to anticancer immunotherapy, we genetically engineered a fusion protein coupling IL-2 and the ectodomain of TGFβ receptor II (Fusion of Interleukin-2 and Soluble TGFβ receptor - a.k.a. FIST). FIST possesses intriguing gain-of-function properties and induces potent activation of IL2-receptor expressing cells and inhibits tumor-derived angiogenesis. Thus FIST constitutes a first-in-class biological that couples anti-angiogenesis to an immune antitumor response.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Schematic representation of FIST mechanism of action. Through IL-2 moiety, FIST induces the activation of IL-2 receptor expressing immune cells, whereas the sTβRII moiety functions as decoy receptor blocking tumor-derived TGFβ-mediated suppression on immune cells.
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Figure 1: Figure 1. Schematic representation of FIST mechanism of action. Through IL-2 moiety, FIST induces the activation of IL-2 receptor expressing immune cells, whereas the sTβRII moiety functions as decoy receptor blocking tumor-derived TGFβ-mediated suppression on immune cells.

Mentions: We have previously demonstrated that the fusion two cytokines with different bioactivities not only recapitulate synergistic effects but also possess unheralded biopharmaceutical properties not seen by the simple combined use of each moiety.9 Similarly, the fusion of IL-2 and sTβRII not only promote activation of IL-2 receptor expressing cells but also blocks tumor derived TGFβ-mediated suppression in these cell compartments (Fig. 1).


FIST, a sword and shield fusokine for cancer immunotherapy.

Penafuerte C, Galipeau J - Oncoimmunology (2012)

Figure 1. Schematic representation of FIST mechanism of action. Through IL-2 moiety, FIST induces the activation of IL-2 receptor expressing immune cells, whereas the sTβRII moiety functions as decoy receptor blocking tumor-derived TGFβ-mediated suppression on immune cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376982&req=5

Figure 1: Figure 1. Schematic representation of FIST mechanism of action. Through IL-2 moiety, FIST induces the activation of IL-2 receptor expressing immune cells, whereas the sTβRII moiety functions as decoy receptor blocking tumor-derived TGFβ-mediated suppression on immune cells.
Mentions: We have previously demonstrated that the fusion two cytokines with different bioactivities not only recapitulate synergistic effects but also possess unheralded biopharmaceutical properties not seen by the simple combined use of each moiety.9 Similarly, the fusion of IL-2 and sTβRII not only promote activation of IL-2 receptor expressing cells but also blocks tumor derived TGFβ-mediated suppression in these cell compartments (Fig. 1).

Bottom Line: FIST).FIST possesses intriguing gain-of-function properties and induces potent activation of IL2-receptor expressing cells and inhibits tumor-derived angiogenesis.Thus FIST constitutes a first-in-class biological that couples anti-angiogenesis to an immune antitumor response.

View Article: PubMed Central - PubMed

Affiliation: The Rosalind & Morris Goodman Cancer Research Centre; McGill University; Montreal, QC Canada.

ABSTRACT
To antagonize tumor-derived TGFβ contemporaneously to anticancer immunotherapy, we genetically engineered a fusion protein coupling IL-2 and the ectodomain of TGFβ receptor II (Fusion of Interleukin-2 and Soluble TGFβ receptor - a.k.a. FIST). FIST possesses intriguing gain-of-function properties and induces potent activation of IL2-receptor expressing cells and inhibits tumor-derived angiogenesis. Thus FIST constitutes a first-in-class biological that couples anti-angiogenesis to an immune antitumor response.

No MeSH data available.


Related in: MedlinePlus