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Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma

Award Number: U01CA232490
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma - PROJECT SUMMARY/ABSTRACT A solid Consortium project should contribute a unique and compelling approach to neuroblastoma and supply tools or components that enable other members of the Consortium to make their best work even better. The project detailed here commences with the selection and careful characterization of a dozen fully human antibodies to Glypican-2, the most promising antigen in neuroblastoma, from a pre-existing hybridoma stock. These antibodies, along with their full sequences, binding affinities, cellular internalization, epitope, and (where possible) crystal structures, will be made available to Consortium members within the first year for use in their modality of choice. This project will explore their utility as components in double bispecific antibody therapy: this double bispecific approach targets two cancer antigens and two T cell receptors simultaneously, inducing T cell activation and co-activation only in the presence of cancer cells expressing both antigens. The double targeting strategy should allow for a much higher level of selective engagement and killing than has heretofore been possible with therapies that target only a single cancer antigen, and should it prove effective in neuroblastoma the approach is likely to have utility in a wide variety of cancers. One historical weakness for the development of immuno-oncology approaches such as this one is that the animal models have had very little predictive value. For this reason, the best of the humanized mouse models, “MISTRG” mice, will be used both for the development of these molecules and for testing the other consortium members’ approaches, where they could be useful. CIVO multi- needle array technology will be employed to simplify the combinatorial challenge associated with testing pairs of bispecific molecules; this technology will also be open for use collaboratively with the other Consortium members. In short, the proposal provides the Consortium with human antibodies against a validated neuroblastoma target, access to the current state-of-the-art in humanized mice, a CIVO multi-needle array device to facilitate testing therapeutics, and a double bispecific antibody therapeutic approach that promises a high level of T cell killing and selectivity and a likely broad applicability beyond neuroblastoma.


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 = -$1 )
2025	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	10/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1
														Subtotal = -$1

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	2	6/14/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $46,597 )
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	003	1	4/22/2022	SUPPLEMENT FOR EXPANSION	-$44,683
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	1	2/2/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	005	2	8/19/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	2/2/2022	NEW	-$656,083
2022	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	004	2	4/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$44,683
2022	2018	SEATTLE CHILDREN'S HOSPITAL	4800 SAND POINT WAY NE	SEATTLE	WA	98105	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	2	2/2/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$702,680
														Subtotal = $46,597

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	1	6/25/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	10/21/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $176,000 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	8/13/2020	SUPPLEMENT FOR EXPANSION	$176,000
2020	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	1	9/3/2020	NEW	$0
														Subtotal = $176,000

Issue Date FY: 2018 ( Subtotal = $2,200,000 )
2018	2018	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	9/10/2018	NEW	$2,200,000
														Subtotal = $2,200,000

Grand Total All Awards = $2,422,596

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Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma

Award Number: U01CA232490

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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