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Harnessing Cytomegalovirus (CMV)-specific T-cells for pancreatic cancer immunotherapy

Award Number: R21CA286198
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/22/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Harnessing Cytomegalovirus (CMV)-specific T-cells for pancreatic cancer immunotherapy - Abstract Immunotherapy is a promising therapeutic strategy for many cancers. Anti-tumor immune responses are elicited against neoantigens that arise from genetic alterations within tumor cells that give rise to a repertoire of peptides that the immune system recognizes as non-self and attack, killing the tumor cells harboring them. Cancers with a high mutational load generally benefit from immune checkpoint therapy, but some solid malignancies, like pancreatic cancer, have a low mutational burden that hampers immunotherapy. One strategy to overcome this limitation is to deliver exogenous neoantigens to cancer cells. Here we propose an approach that uses the tumor penetrating peptide iRGD, to deliver neoantigens to pancreatic tumors. Unlike conventional RGD peptides, iRGD, is not only able to target and the tumor vasculature through αv integrin, but also to extravasate and penetrate tumor tissue via neuropilin-1 delivering conjugated or co-administered drugs or peptides. Pancreatic cancer long term survivors often have neoantigens that mimic common viral epitopes, suggesting the possibility that these individuals benefited from an immune response against neoantigens that mimic viral components. We posit that iRGD-mediated delivery of these antigens to pancreatic tumors will redirect pre-existing antiviral immunity against them. For this purpose, we will use peptides activating cytomegalovirus (CMV)-specific T cells. CMV is a β-herpesvirus infects >60% of the population and elicits a strong immune response accounting for >10% of all circulating CD4 and CD8 T cells. Our preliminary data show that mice latently infected with CMV containing orthotopic pancreatic tumors respond to treatment with iRGD plus CMV peptides with tumor regression associated to increased necrosis, and marked T cell infiltration. Here we propose experiments to determine in an orthotopic pancreatic tumor mouse model, what are the best neoantigens and the optimal treatment conditions for achieving long lasting tumor regression (Aim 1). We will also assess the presence of CMV specific T cells in human pancreatic tumors, a necessary step toward the eventual translatability of this approach (Aim 2).


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 = $190,283 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	2	11/19/2024	NON-COMPETING CONTINUATION	$171,255
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	001	2	5/29/2025	NON-COMPETING CONTINUATION	$19,028
														Subtotal = $190,283

Issue Date FY: 2024 ( Subtotal = $242,178 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Cancer Treatment Research	000	1	12/22/2023	NEW	$242,178
														Subtotal = $242,178

Grand Total All Awards = $432,461

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Harnessing Cytomegalovirus (CMV)-specific T-cells for pancreatic cancer immunotherapy

Award Number: R21CA286198

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/22/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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