This list back in play? Wouldn't it be surprising if GILD ended up in the catbird seat for checkpoint inhibition?
GILD - Idelalisib
INCY - INCB40093
TGTX - TGR-1202
INFI - IPI-145 and IPI-443
Any others?
Message 29582520
Nature. 2014 Jun 11. doi: 10.1038/nature13444. [Epub ahead of print]
Inactivation of PI(3)K p110d breaks regulatory T-cell-mediated immune tolerance to cancer.
Ali K1, Soond DR2, Piñeiro R1, Hagemann T3, Pearce W4, Lim EL5, Bouabe H5, Scudamore CL6, Hancox T7, Maecker H8, Friedman L8, Turner M5, Okkenhaug K9, Vanhaesebroeck B1.
11] UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK [2].
21] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2] [3].
3Centre for Cancer and Inflammation, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
4UCL Cancer Institute, Paul O'Gorman Building, University College London, 72 Huntley Street London WC1E 6DD, UK.
5Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
6Mary Lyon Centre, MRC Harwell, Harwell Science and Innovation Campus, Harwell OX11 0RD, UK.
7Piramed Pharma, 957 Buckingham Avenue, Slough, Berkshire SL1 4NL, UK.
8Cancer Signaling and Translational Oncology, Genentech Inc, 1 DNA Way, South San Francisco, California 94080-4990, USA.
91] Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK [2].
Inhibitors against the p110d isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110d is primarily expressed in leukocytes, drugs against p110d have not been considered for the treatment of solid tumours. Here we report that p110d inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110d inactivation in regulatory T?cells unleashes CD8+ cytotoxic T?cells and induces tumour regression. Thus, p110d inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology. |
