Unbiased in vivo CRISPR screen to identify novel T-cell immune checkpoints for cancer immunotherapy (360G-Wellcome-210910_Z_18_Z)

£250,000

Harnessing the anti-tumour potential of T-cells for cancer treatment has been successful for a number of malignancies. The blockade of immune checkpoints, such as the T-cell receptor PD-1, reduces tumour burden in patients and can lead to durable cures for some. Treatment efficiency is further improved when PD-1 is targeted simultaneously with other checkpoints such as CTLA4 or LAG3. Despite the potential of co-targeting multiple checkpoints, the combinatorial co-inhibition of all known as well as yet undiscovered immune checkpoints has not been systematically assessed. Furthermore, genome-wide screening to identify novel checkpoints as well as modifiers of such checkpoints has been technically challenging. The objective of this proposal is to map the combinatorial landscape of known checkpoints coupled with PD-1 blockade as well as discover potentially new targets for immune activation against cancer. We propose to use of transplanted hematopoietic stem cells with different combinations of disabled T-cell surface proteins to screen for combinations which enable T-cell infiltration and tumour reduction in a PD-1 suppressed mouse melanoma model. Initially combinations of known checkpoints will be assessed, subsequently the screen will be expanded to all T-cell membrane proteins to identify novel immune checkpoints.

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Grant Details

Amount Awarded 250000
Applicant Surname Tomberg
Approval Committee Basic Science Interview Committee
Award Date 2018-04-24T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Sir Henry Wellcome Postdoctoral Fellowship
Internal ID 210910/Z/18/Z
Lead Applicant Dr Kärt Tomberg
Partnership Value 250000
Planned Dates: End Date 2022-07-15T00:00:00+00:00
Planned Dates: Start Date 2018-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Allan Bradley