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Functional characterization of dendritic cell heterogeneity for T cell-inducing immunotherapies

Award Number: DP2AI201038
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: 08/03/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Functional characterization of dendritic cell heterogeneity for T cell-inducing immunotherapies - Project Summary/Abstract The deliberate harnessing of human immunity has revolutionized modern medicine, with vaccine innovation and global deployment representing the most effective interventions against infectious diseases. Many current vaccine strategies offer protection by inducing antibody responses. But for important infectious diseases caused by intracellular pathogens, including HIV/AIDS and malaria, even a robust antibody response is not sufficient to provide full protection. The eliminating of these pathogens requires the generation of potent and durable cytotoxic T lymphocyte responses, which are not efficiently induced by current vaccine technologies. It has been well established that the type 1 conventional dendritic cells (cDC1) play indispensable roles in activating anti-viral and anti-tumor T cell responses. Thus, dendritic cells have become key targets for T cell- inducing vaccine development. Compared to cDC1, the functions of type 2 conventional dendritic cells (cDC2) are less well understood, largely due to the lack of selective lineage-depletion mouse model. We recently generated a first mouse model that completely ablates cDC2 development. Studies with this mouse model showed that, unexpectedly, cDC2-deficient mice display enhanced anti-viral responses to LCMV Clone-13. For treating both infectious diseases and cancers, a number of strategies that target dendritic cells for inducing cytotoxic T lymphocyte responses have been or are being investigated. But unfortunately, the majority result in low level, non-protective responses. It turns out that most T cell-inducing vaccine platforms target both cDC1 and cDC2. We hypothesize that the primary reason current vaccine strategies fail to induce potent and durable cytotoxic T lymphocyte responses is the underappreciation of functional heterogeneity among antigen- presenting cells, particularly dendritic cells. We propose to characterize the functional heterogeneity of antigen- presenting cells in regulating anti-viral T cell responses, elucidate the underlying mechanism(s) driving the functional heterogeneity of antigen-presenting cells (Aim 1), and assess whether these mechanisms also apply to anti-tumor T cell responses (Aim 2). The central question driving our research is: to effectively induce potent and durable cytotoxic T lymphocyte responses, which antigen-presenting cell subset(s) should be targeted, and which should be avoided.


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: 2026 ( Subtotal = $552,000 )
2026	2026	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	7/28/2026	NEW	$552,000
														Subtotal = $552,000

Grand Total All Awards = $552,000

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Functional characterization of dendritic cell heterogeneity for T cell-inducing immunotherapies

Award Number: DP2AI201038

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: 08/03/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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