Avoiding on-target off-tumour toxicity in cancer immunotherapy. (360G-Wellcome-110022_Z_15_Z)

£275,672

Chimeric antigen receptors link MHC-unrestricted antigen specificity with T-cell signalling, facilitating potent and regulatable antigen-specific cancer recognition and killing. Clinical trials of CAR gene modified T-cells show unprecedented clinical responses, with the major limitation of on-target off-tumour toxicity due to expression of most cancer antigens on some normal tissues. In my Wellcome clinical training fellowship I identified a novel method of avoiding such toxicity by designing CA Rs for use in gdT-cells. These gdT-CAR cells combine innate killing limited to sites of cancer or injury with CARs providing co-stimulation to overcome the immunoinhibitory tumour microenvironment. I demonstrated proof of concept using two model antigens, GD2 and CD33, applicable to solid cancers (e.g. neuroblastoma) and myeloid leukaemias (e.g. AML) respectively. In my fellowship I will develop this by: 1) Identifying mechanism and relative efficacy of different co-stimulatory CAR endodomains in gdT cells 2) Investigate selectivity of co-stimulatory CARs in gdT against acute myeloid leukaemia compared with healthy blood cells bearing the same tissue antigen. 3) Investigate the use of mass cytometry for high-dimensional signalling analysis to inform CAR design. Efficacy, toxicity and mechanism will be assessed in a staged manner using cell lines and primary tissue.

Where is this data from?

This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.

Grant Details

Amount Awarded 275672
Applicant Surname Fisher
Approval Committee Clinical Interview Committee
Award Date 2015-11-19T00:00:00+00:00
Financial Year 2015/16
Grant Programme: Title Postdoctoral Training Fellowship for Clinicians
Internal ID 110022/Z/15/Z
Lead Applicant Dr Jonathan Fisher
Partnership Value 275672
Planned Dates: End Date 2019-08-31T00:00:00+00:00
Planned Dates: Start Date 2016-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof John Anderson