Dr Jonathan Fisher
My team investigates novel engineering approaches in gdT cells. By harnessing and enhancing their innate anti-cancer properties, we hope to improve their efficacy against a range of tumour types. Focusing on the immunological mechanics has been particularly rewarding as it has allowed us to develop local and international collaborations with colleagues investigating both solid and haematological malignancies in children and adults, rather than being restricted to a single disease type.
The evolution of higher parameter single-cell analysis is facilitating greater understanding of the interplay between cancer and the immune system, and there is an increasing expectation that novel technologies are firmly grounded in mechanistic analysis. It is increasingly necessary to be able to demonstrate not only whether an immunotherapeutic works, but also how, so that bottlenecks and barriers can be overcome at the preclinical stage.
The mechanistic techniques used in my laboratory help to address some of these issues. By dissecting the cellular events that underpin the activity of immunotherapeutics, we can create novel means of overcoming bottlenecks and increase the chances of a novel therapy working in the clinic.
Clinical Applications of Cell & Gene Therapy – Module co-director
- Group members
Dr Marta Barisa
IRIS profile: Marta Barisa
Dr Daniel Fowler
IRIS profile: Daniel Fowler
IRIS profile: Alba Southern
IRIS profile: Callum Nattress
- Selected Publications
- Fisher. J., Sharma. R., Don, N., Barisa. M., Hurtado. M., Abramowski, P., Porter. L., Day. W., Borea. R., Inglott. S., Anderson. J., Pe’er. D. Single cell signaling analysis provides mechanistic context for chimeric antigen receptor design in cancer immunotherapy. Science Signalling, 10/09/2019, 12(598).
- Ollé Hurtado. M., Wolbert. J., Fisher. J., Flutter. B., Stafford. S., Barton. J., Jain. N., Barone. G., Majani. Y., Anderson. J. Tumor infiltrating lymphocytes expanded from pediatric neuroblastoma display heterogeneity of phenotype and function. PLoS One. 2019 Aug 9;14(8):e0216373. doi: 10.1371/journal.pone.0216373.
- Fisher J and Anderson J (2018) Engineering Approaches in Human Gamma Delta T Cells for Cancer Immunotherapy. Front. Immunol. 9:1409. doi: 10.3389/fimmu.2018.01409
- Capsomidis. A, Benthall. G, Van Acker. H, Fisher. J, Kramer. A, Abeln. Z, Majani. Y, Gileadi. T, Wallace. R, Gustafsson. K, Flutter. B, Anderson. J. Chimeric Antigen Receptor-Engineered Human Gamma Delta T Cells: Enhanced Cytotoxicity with Retention of Cross Presentation. Mol. Ther. 26, 354–365 (2018).
- Fisher. J, Abramowski. P, Wisidagamage Don. N, Flutter. B, Capsomidis. A, Cheung. G, Gustafsson. K, Anderson. J. Avoidance of On-Target Off-Tumor Activation Using a Co-stimulation-Only Chimeric Antigen Receptor. Molecular Therapy 25(5), 1-14 (2017) PMID 28341563
- Fisher J, Flutter B, Wesemann F, Frosch J, Rossig C, Gustafsson K, Anderson J. Effective combination treatment using anti-GD2 ch14.18/CHO antibody with Vd2+ gdT cells in Ewing sarcoma and neuroblastoma. Oncoimmunology 2015 Apr 27;5(1):e1025194
- Fisher J, Gustafsson. K, Anderson. J. Non-V delta 2 gamma delta T lymphocytes as effectors of cancer immunotherapy. Oncoimmunology (4) 3; 2015
- Fisher J, Yan M, Heuijerjans J, Carter L, Abolhassani A, Frosch J, Wallace R, Flutter B, Hubank M, Klein N, Callard R, Gustafsson K, Anderson J. Neuroblastoma killing properties of V-delta 2 and V-delta2 negative gamma delta T cells following expansion by artificial antigen presenting cells. Clin Cancer Res. 2014 Jun 3
- Gustafsson K, Anderson J, Fisher J, Yan M. Regeneration of stalled immune responses to transformed and infected cells using γδ T cells. Drug Discovery Today. 2014 Jun;19(6):787-793
- Fisher. J, Heuijerjans. J, Yan. M, Gustafsson. K, Anderson. J. gdT cells for cancer immunotherapy: A systematic review of clinical trials. Oncoimmunology (3) 17th Jan 2014