Wednesday, July 16, 2025 7/16/2025

SARS-CoV-2-reactive tissue-resident memory T cells in healthy and cancer subjects

Award Number: U01CA260588
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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SARS-CoV-2-reactive tissue-resident memory T cells in healthy and cancer subjects - PROJECT SUMMARY This multi-PI proposal titled “SARS-CoV-2-reactive subjects” is written in response to ‘RFA-CA-20-039’ - tissue-resident memory T cells in healthy and cancer Research projects in SARS-CoV-2 Serological Sciences. Recent studies have shown that antibody responses to SARS-CoV-2 infection decline rapidly over time, implying a lack of durable protective humoral (B cell) immunity. Whether this is also true for cellular immunity (e.g., T cells) is poorly understood. It is well established that CD8+ TRM cells are the first line of defense in viral infections at mucosal/barrier sites. They are also known to protect hosts against homologous or heterologous re-infections. Our group was the first to show that TRM cells are pivotal players in driving effective anti-tumor immune responses in lung cancer, and that TRM cells are the primary cellular targets of anti-PD1 therapies. These key findings were possible because of the ongoing collaboration between Dr. Vijayanand, Dr. Ay, and Dr. Ottensmeier (Multi-PI). This team brings together experience in T cell immunology, single-cell genomics, bioinformatics, and cancer immunology. Our Multi-PI team has recently performed the first and largest single-cell RNA-seq and TCR-seq analysis of SARS-CoV-2-reactive CD8+ and CD4+ T cells (~300,000 single-cells) from COVID-19 patients. Here, to understand TRM responses to SARS-CoV-2, we will capitalize on a cohort of cancer (n=100) and non-cancer (n=100) patients, who will provide excess airway (nasal, oropharynx, larynx), lung and tumor tissue specimens obtained during routine surgery. In AIM 1, we will define the properties of SARS-CoV-2 reactive TRM cells from cancer and non-cancer patients with or without previous SARS-CoV-2 infection. We will perform combined single-cell RNA-seq and TCR-seq analysis of CD8+ TRM cells in the airways (nasal, oropharynx), lung, and tumor tissue. In parallel, by stimulating PBMCs with SARS-CoV-2 peptide pool, we will determine the transcriptomic and TCR sequence of SARS-CoV-2 reactive T cells. We will utilize this TCR sequence information to define the numbers and properties of SARS-CoV-2 reactive-TRM cells in mucosal and tumor tissues. Recent studies in non- exposed individuals (pre-COVID-19 pandemic) indicate pre-existing, circulating CD8+ T cells, with human coronavirus cross-reactivity. Here, we will measure the quantity and quality of pre-existing SARS-CoV-2 cross- reactive TRM responses in subjects without clinical or serological evidence of previous SARS-CoV-2 infection. In AIM 2, we will assess the impact of SARS-CoV-2 infection on anti-tumor and other anti-viral TRM responses. We will stimulate matched PBMCs (as above) with peptide pools targeting (i) common respiratory RNA viruses (influenza (FLU), RSV), (ii) persistent DNA viruses (CMV, EBV), and (iii) a tumor-driving virus (HPV) to define the TCR sequence of the respective virus-specific and tumor(HPV)-specific CD8+ T cells; we will utilize the TCR information to determine frequency and properties of other virus/tumor-reactive TRM cells in mucosal and tumor- tissue cells.


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	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	005	2	4/7/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2024	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	003	2	3/27/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	002	2	3/27/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	004	2	4/7/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	2	3/27/2025	EXTENSION WITH OR WITHOUT FUNDS	$0
2025	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	006	2	4/8/2025	EXTENSION WITH OR WITHOUT FUNDS	$0
2025	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	1	3/13/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $293,085 )
2024	2024	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	002	2	8/20/2024	SUPPLEMENT FOR EXPANSION	$293,085
2024	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	2	8/20/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	2	8/20/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $293,085

Issue Date FY: 2023 ( Subtotal = $1,130,292 )
2023	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	2	6/2/2023	SUPPLEMENT FOR EXPANSION	$1,130,292
2023	2023	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	002	2	6/21/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	2	6/21/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $1,130,292

Issue Date FY: 2022 ( Subtotal = $732,439 )
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	002	2	9/16/2022	EXTENSION WITH OR WITHOUT FUNDS	$732,439
2022	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	001	1	12/8/2021	NEW	$0
2022	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	1	12/7/2021	NEW	$0
														Subtotal = $732,439

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	1	12/30/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,446,305 )
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cancer Detection and Diagnosis Research	000	1	9/21/2020	NEW	$1,446,305
														Subtotal = $1,446,305

Grand Total All Awards = $3,602,121

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SARS-CoV-2-reactive tissue-resident memory T cells in healthy and cancer subjects

Award Number: U01CA260588

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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