Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Towards Translation of MU-CN29: New Therapeutic Nanoparticle for Drug-Resistant NSCLC

Award Number: R01CA274677
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/17/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2027

Group Awards By:

View Award Description

Towards Translation of MU-CN29: New Therapeutic Nanoparticle for Drug-Resistant NSCLC - ABSTRACT Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality in both men and women. Despite rapid therapeutic advances, the 5-year survival rate of EGFR-mutant NSCLC remains a dismal 16% for the past several decades. In particular, the rapid emergence of resistance to widely used treatments, such as the tyrosine kinase inhibitor (TKI), is the key obstacle to achieving long-term NSCLC patient survival. Further, patients with EGFR mutated tumors fail to respond to immune checkpoint inhibitors (ICIs), leaving them with little to no hope of a long-term remission. Therefore, identifying the molecular determinants of resistance and developing a therapeutic that targets the chemo- and immune-resistant pathways, is the best chance to improve survival rates in NSCLC patients with an EGFR mutation. We hypothesize that MU-CN29, the lead targeted siRNA nanoconjugate, restores sensitivity to tyrosine kinase inhibitors in resistant NSCLC. We further postulate that MU-CN29 will induce a systemic immune response, priming the tumor microenvironment for immunotherapy via ICIs. Therefore, the central objective of this TTNCI proposal is to develop, evaluate, and validate MU-CN29 as an effective therapeutic agent for resistant NSCLC. Our promising in vitro and in vivo experimental results confirmed the crosstalk between the resistance-driving receptor tyrosine kinase AXL and FN14 pathways in drug resistant NSCLC. Additionally, we found that the co-knockdown of both AXL and FN14, using MU-CN29, covalently attached with the dual siRNAs, sensitized the resistant tumors to tyrosine kinase inhibitor (TKI), in vitro and in vivo. To enable translation of MU-CN29 to human trials, in this proposal, we will manufacture the nanoparticles as per FDA guidelines, perform detailed toxicology studies in murine and canine subjects, and evaluate the therapeutic efficacy in clinically relevant animal models. The specific aims of this applications are: (1) Determine MU-CN29 clinical-grade production protocols; (2) Determine the safety and efficacy of MU-CN29 in murine NSCLC models; (3) Establish safety of MU-CN29 in canine cancer patients. The data will validate MU-CN29 nanoparticle platform as a promising strategy to combat drug resistance in NSCLC and catalyze clinical trials in the future.


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 MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	4	3/19/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $563,952 )
2025	2025	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	4	6/3/2025	NON-COMPETING CONTINUATION	$563,952
														Subtotal = $563,952

Issue Date FY: 2024 ( Subtotal = $545,975 )
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	3	5/22/2024	NON-COMPETING CONTINUATION	$545,975
														Subtotal = $545,975

Issue Date FY: 2023 ( Subtotal = $578,421 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	2	5/17/2023	NON-COMPETING CONTINUATION	$578,421
														Subtotal = $578,421

Issue Date FY: 2022 ( Subtotal = $622,068 )
2022	2022	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Cancer Treatment Research	000	1	6/17/2022	NEW	$622,068
														Subtotal = $622,068

Grand Total All Awards = $2,310,416

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Towards Translation of MU-CN29: New Therapeutic Nanoparticle for Drug-Resistant NSCLC

Award Number: R01CA274677

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/17/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer