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Removing sialic acid ligands of CD28 to enhance T cell cancer immunotherapy

Award Number: R21AI171628
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/17/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2025

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Removing sialic acid ligands of CD28 to enhance T cell cancer immunotherapy - Summary T cells play a central role in the adaptive immune system and are activated in response to T cell receptor (TCR) recognition of antigen loaded on the major-histocompatibility complex (MHC) of antigen presenting cells (APCs). In order to fully achieve T cell effector function, an essential “second signal” is provided by engagement of the T cell costimulatory receptor CD28 with its B7 ligands (CD80/CD86) on the APC. We recently demonstrated that sialic acids on T cells and APCs dampen CD28 binding to CD80/CD86 and that removal of sialic acids with sialidase enhances T cell proliferation. Sialic acid removal is also synergistic with programmed cell death protein-1 (αPD1) checkpoint inhibitor blockade for functional revival of exhausted T cells. In this project, we will develop bifunctional αPD1-sialidase conjugates that are expected to combine the benefits of PD1 blockade with removal of sialic acid ligands of CD28 to promote engagement with B7 ligands and enhance T cell activation. We will evaluate these reagents in animal models of cancer for their therapeutic potential to invigorate exhausted T cells and suppress cancer progression.


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	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	6/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $271,500 )
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	2	1/23/2024	NON-COMPETING CONTINUATION	$244,350
2024	2024	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	5/22/2024	NON-COMPETING CONTINUATION	$27,150
														Subtotal = $271,500

Issue Date FY: 2023 ( Subtotal = $226,250 )
2023	2023	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	2/17/2023	NEW	$226,250
														Subtotal = $226,250

Grand Total All Awards = $497,750

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Removing sialic acid ligands of CD28 to enhance T cell cancer immunotherapy

Award Number: R21AI171628

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/17/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2025

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