A high percentage of regulatory T cells (Tregs) among tumour-infiltrating lymphocytes weakens the immune response against tumours. The anergy of effector T cells (Teff) can be reversed by immune checkpoint treatment, which inhibits Tregs and boosts the activation of Teff. Both effects can be obtained by triggering the glucocorticoid-induced TNF related (GITR) receptor, a co-stimulatory molecule expressed by Teff and Tregs, and by inhibiting the programmed cell death (PD)-1 receptor, an inhibitory molecule expressed by Teff. Patent W02015/026684A1 provides a method of treating human tumours using a combination of a molecule triggering GITR and another inhibiting PD-1. The treatment approach was tested on three murine models of cancer, and the synergic effect of anti-human antibodies (Abs) in combination was tested in mixed lymphocyte reactions. Immune checkpoint treatment can break tolerance towards tumours and promote tumour rejection. The patented approach is very interesting and might be successful. The combined use of PD-1 antagonists and GITR agonists is synergic and tumour-centred, and adverse events might be less problematic than expected. A crucial point in translating the murine studies to humans is the differences between murine and human GITR and the evidence that some anti-human GITR Abs are not agonists

Modulation of tumour immunity: a patent evaluation of WO2015026684A1

NOCENTINI, Giuseppe;CARI, LUIGI;RONCHETTI, Simona;RICCARDI, Carlo
2016

Abstract

A high percentage of regulatory T cells (Tregs) among tumour-infiltrating lymphocytes weakens the immune response against tumours. The anergy of effector T cells (Teff) can be reversed by immune checkpoint treatment, which inhibits Tregs and boosts the activation of Teff. Both effects can be obtained by triggering the glucocorticoid-induced TNF related (GITR) receptor, a co-stimulatory molecule expressed by Teff and Tregs, and by inhibiting the programmed cell death (PD)-1 receptor, an inhibitory molecule expressed by Teff. Patent W02015/026684A1 provides a method of treating human tumours using a combination of a molecule triggering GITR and another inhibiting PD-1. The treatment approach was tested on three murine models of cancer, and the synergic effect of anti-human antibodies (Abs) in combination was tested in mixed lymphocyte reactions. Immune checkpoint treatment can break tolerance towards tumours and promote tumour rejection. The patented approach is very interesting and might be successful. The combined use of PD-1 antagonists and GITR agonists is synergic and tumour-centred, and adverse events might be less problematic than expected. A crucial point in translating the murine studies to humans is the differences between murine and human GITR and the evidence that some anti-human GITR Abs are not agonists
2016
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1367452
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