TGF-β1 potentiates Vγ9Vδ2 T cell adoptive immunotherapy of cancer.
| Autor: | Beatson RE; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Parente-Pereira AC; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Halim L; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Cozzetto D; Translational Bioinformatics, NIHR Biomedical Research Centre, Guy's and St. Thomas's NHS Foundation Trust and King's College London, London SE1 9RT, UK., Hull C; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Whilding LM; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Martinez O; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Taylor CA; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Obajdin J; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Luu Hoang KN; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Draper B; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Iqbal A; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK.; Cancer Bioinformatics, King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Hardiman T; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK.; Cancer Bioinformatics, King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Zabinski T; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Man F; King's College London, School of Biomedical Engineering and Imaging Sciences, St. Thomas' Hospital, London SE1 7EH, UK., de Rosales RTM; King's College London, School of Biomedical Engineering and Imaging Sciences, St. Thomas' Hospital, London SE1 7EH, UK., Xie J; Bayer Healthcare Innovation Center, Mission Bay, 455 Mission Bay Boulevard South, San Francisco, CA 94158, USA., Aswad F; Bayer Healthcare Innovation Center, Mission Bay, 455 Mission Bay Boulevard South, San Francisco, CA 94158, USA., Achkova D; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Joseph CR; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Ciprut S; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Adami A; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Roider HG; Bayer AG, Müllerstrasse 178, 13342 Berlin, Germany., Hess-Stumpp H; Bayer AG, Müllerstrasse 178, 13342 Berlin, Germany., Győrffy B; Department of Bioinformatics, Semmelweis University, Budapest H1085, Hungary.; Cancer Biomarker Research Group, Research Center for Natural Science, Budapest H1117, Hungary., Quist J; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK.; Cancer Bioinformatics, King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Grigoriadis A; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK.; Cancer Bioinformatics, King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Sommer A; Bayer AG, Müllerstrasse 178, 13342 Berlin, Germany., Tutt ANJ; King's College London, Breast Cancer Now Unit, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Davies DM; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK., Maher J; King's College London, School of Cancer and Pharmaceutical Sciences, Guy's Cancer Centre, Great Maze Pond, London SE1 9RT, UK.; Department of Immunology, Eastbourne Hospital, Kings Drive, Eastbourne, East Sussex BN21 2UD, UK.; Department of Clinical Immunology and Allergy, King's College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK.; Leucid Bio, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. |
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| Jazyk: | angličtina |
| Zdroj: | Cell reports. Medicine [Cell Rep Med] 2021 Dec 21; Vol. 2 (12), pp. 100473. Date of Electronic Publication: 2021 Dec 21 (Print Publication: 2021). |
| DOI: | 10.1016/j.xcrm.2021.100473 |
| Abstrakt: | Despite its role in cancer surveillance, adoptive immunotherapy using γδ T cells has achieved limited efficacy. To enhance trafficking to bone marrow, circulating Vγ9Vδ2 T cells are expanded in serum-free medium containing TGF-β1 and IL-2 (γδ[T2] cells) or medium containing IL-2 alone (γδ[2] cells, as the control). Unexpectedly, the yield and viability of γδ[T2] cells are also increased by TGF-β1, when compared to γδ[2] controls. γδ[T2] cells are less differentiated and yet display increased cytolytic activity, cytokine release, and antitumor activity in several leukemic and solid tumor models. Efficacy is further enhanced by cancer cell sensitization using aminobisphosphonates or Ara-C. A number of contributory effects of TGF-β are described, including prostaglandin E Competing Interests: J.M. is chief scientific officer, scientific founder, and shareholder of Leucid Bio; is a member of the scientific advisory board of Suda Pharmaceutics; and has undertaken consultancy work for Bristol-Meyers-Squibb, Juno, Celgene, Ellipses Pharma, and Biotest. A.C.P.-P. is currently an employee of GlaxoSmithKline. L.H. and B.D. undertook Ph.D. studentships funded by Leucid Bio. C.H. and D.M.D are currently employees of Leucid Bio. L.M.W. and D.M.D. were formerly consultants to Leucid Bio. L.M.W. is currently an employee of Oxford Biomedica. T.Z. is currently an employee of Orchard Therapeutics. J.X., F.A., and A.S. were formerly employees of Bayer AG. A.S. is a shareholder of Bayer AG. J.M., A.C.P.-P., and R.E.B. are co-inventors on patent filings in relation to the manufacture of γδ T cells in the presence of TGF-β. C.-Y.R.J. is currently an employee of TCR2 Therapeutics. H.G.R. and H.H.-S. are employees of Bayer AG. B.D. and D.A. are shareholders of Autolus Therapeutics. D.A. is a former employee of Autolus Therapeutics. F.M. and R.T.M.d.R. are co-inventors on patent filings in relation to the manufacture of 89Zr-oxine for cell labeling. A.N.J.T. is/has been a consultant for AstraZeneca, Merck KGaA, Artios, Pfizer, Vertex, GE Healthcare, Inbiomotion, and MD Anderson Cancer Center; has received grant/research support from AstraZeneca, Myriad, Medivation, and Merck KGaA; is a stockholder in Inbiomotion; and stands to gain from the use of PARP inhibitors as part of the ICR’s “rewards to inventors” scheme. The other authors declare no competing interests. (© 2021 The Author(s).) |
| Databáze: | MEDLINE |
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