Wednesday, December 31, 2025 12/31/2025

Engineering viral nanoparticles for TLR agonist-based multi-functional cancer immunotherapies

Award Number: R00CA283299
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Engineering viral nanoparticles for TLR agonist-based multi-functional cancer immunotherapies - PROJECT SUMMARY/ABSTRACT Ovarian cancer is the most lethal gynecologic malignancy for women; standard of care surgery and chemotherapy treatment can provide a short period of remission but cannot eradicate the disease and prevent recurrence. Cancer immunotherapy has shown great potential in treating cancers, but no clinical success has been reported for ovarian cancer. One major hurdle for cancer immunotherapy that is needed to overcome is to convert the immunosuppressive tumor microenvironment (TME). The goal of this proposal is to develop effective nanomedicines that are capable of reprogramming and converting the suppressive TME for ovarian cancer treatment. To achieve this goal, I will utilize viral nanoparticles (VNPs) to incorporate various functionalities targeting different aspects of the TME through bioengineering approaches. The two VNPs that will be used in this proposal are cowpea mosaic virus (CPMV) and hepatitis B virus capsid (HBVc), which both have well-characterized and stable structures for in vitro bioengineering. Toll-like receptor (TLR) agonists have been demonstrated to be potent to activate the innate immune system and modulate the TME. CPMV is a triple TLR 2, 4, and 7 agonist and is effective to reprogram the TME of ovarian cancer. In the mentored K99 phase, I will focus on using CPMV as a triple TLR agonist to develop an adjuvant and antigen combination in-situ vaccine for ovarian cancer treatment (Aim 1) and developing multi-TLR agonists to investigate the mechanism of action (MOA) of CPMV and multi-TLRs activation in cancer treatment to design potent TLR agonists combination for downstream applications (Aim 2). During my independent R00 phase, I will use HBVc as a nanotechnology platform to develop multiple functional therapeutic nanomaterials aiming to reprogram the suppressive TME to treat ovarian cancer and investigate the MOA. First, I will develop HBVc-based TLR agonist and pro-inflammatory cytokine combination therapies, which can exert the functions of reprograming the TME and killing cancer cells concurrently (Aim 3). Secondly, I will develop HBVc into a “smart” nanoparticle that functions as a TLR agonist and targets and converts the pro-tumor M2 macrophages into anti-tumor M1 macrophages (Aim 4). During my graduate study, I have been trained in manipulating HBVc in vitro assembly and genetic engineering of HBVc to design novel structures. In the past two and a half years as a postdoc in Dr. Steinmetz’s lab at UCSD, I have been trained systematically in the bioengineering of VNPs and the application of engineered VNPs for cancer treatment. A further two years of training in Dr. Steinmetz’s lab will allow me to enrich my background in cancer immunology, immune-oncology, and tumor modeling. With the help and guidance from my advisory committee, by the end of my mentored phase, I will be able to secure a tenure-track faculty position in a top-tier research institute to establish my independent research program focusing on using HBVc as a nanotechnology platform to develop novel and effective multi-functional nanomedicines for cancer patients.


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 = $0 )
2026	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Research Manpower	000	3	12/2/2025	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $249,000 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Research Manpower	000	3	9/11/2025	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $249,000

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Engineering viral nanoparticles for TLR agonist-based multi-functional cancer immunotherapies

Award Number: R00CA283299

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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