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NGTC - UCL

Award Number: OT2CA278730
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: OTHER
PERIOD OF PERFORMANCE START DATE: 06/24/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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NGTC - UCL - Next Generation T cell therapies for childhood cancers [NexTGen] Current treatments fail to cure many children with solid cancers. Recent advances in adult cancers such as checkpoint blockade and targeted small molecules have made little impact in childhood disease. Engineered T-cell therapies can achieve durable responses in refractory lymphoid cancers without long-term toxicity. These are precisely the characteristics required for new treatments for pediatric solid cancers. In contrast to hematologic malignancies, solid cancers are challenging due to a lack of targets, tumor heterogeneity, and hostile tumor microenvironment (TME). We posit that through advanced cellular engineering we can overcome these challenges. Our vision is that engineered T-cell therapy for childhood solid cancers will become routine within a decade. Our central hypothesis is that coupling of advanced cellular engineering along with progressive clinical development is the fastest route to developing effective T-cell therapies for pediatric solid tumors. In NexTGen, we combine detailed studies of primary tumors to discover new targets and understand how the TME subverts T- cell function. This, along with a closely coupled clinical development program will guide the progressive engineering of T-cells to result in transformative therapies. NexTGen is composed of 6 inter-connected work-packages (WPs) with work initially focused on pediatric sarcomas and brain tumors. AIMS: WP1: To identify suitable targets for engineered T-cells. WP2: To understand the TME in pediatric solid cancers. WP3: To develop receptors and other engineering components which target tumor cells and resist or modulate the TME. WP4: To evaluate the function of engineered T-cells developed in WP3. WP5: To translate approaches from WP4 and test them in clinical studies designed for maximal impact. Cancer Grand Challenges - Full Application - 2021 WP6: To promote data sharing across all WPs. METHODS: Target discovery (WP1) and TME studies (WP2) will utilize mass spectroscopy and chip cytometry respectively. Component engineering (WP3) will use protein engineering methods. To model engineered cell function, WP4 will mostly use intact tumor models such as immune PDXs. In WP5, clinical product generation will involve autologous closed system semi-automated manufacturing. WP6 uses standard and custom databases and data sharing platforms. USE OF RESULTS: Tumor target and TME data from WP1 and 2 will be uploaded to databases developed by WP6 for widespread distribution. Engineering components from WP3 and functional data from WP4 will be available for incorporation into therapeutic T-cell strategies by the entire community. Clinical study data from WP5 should lead to registration studies, improving cure rates and mitigation of long-term toxicity to realize our Vision.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2022	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	000	1	5/7/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1,100,987 )
2024	2024	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	001	1	9/10/2024	SUPPLEMENT FOR EXPANSION	$1,100,987
2024	2022	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	000	1	6/6/2024	NEW	$0
														Subtotal = $1,100,987

Issue Date FY: 2023 ( Subtotal = $431,742 )
2023	2023	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	001	1	9/1/2023	SUPPLEMENT FOR EXPANSION	$431,742
2023	2022	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	000	1	5/26/2023	NEW	$0
														Subtotal = $431,742

Issue Date FY: 2022 ( Subtotal = $2,095,142 )
2022	2022	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	000	1	6/24/2022	NEW	$1,998,150
2022	2022	UNIVERSITY COLLEGE LONDON	GOWER STREET	LONDON				GBR	Cancer Cause and Prevention Research	001	1	7/12/2022	NEW	$96,992
														Subtotal = $2,095,142

Grand Total All Awards = $3,627,871

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NGTC - UCL

Award Number: OT2CA278730

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: OTHER

PERIOD OF PERFORMANCE START DATE: 06/24/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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