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Development of T cell-mediated targeted gene delivery of immunotoxin in HNSCC

Award Number: R03DE030227
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Development of T cell-mediated targeted gene delivery of immunotoxin in HNSCC - Development of T cell-mediated targeted gene delivery of immunotoxin in HNSCC Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with more than 500,000 new cases diagnosed annually. Chemotherapy, targeted treatment, and immunotherapy have been approved by the FDA for HNSCC treatment. While a minority of patients experience dramatic long-lasting and favorable clinical responses, the majority of patients fail to achieve durable clinical response. Thus, alternative options with improved beneficial response are urgently needed. In HNSCC, over 90% of tumors overexpress cell surface EGFR. Recombinant immunotoxin (RIT) is a fused protein often consisting of an antibody that targets a tumor antigen and a toxin (e.g., diphtheria toxin [DT]) that kills tumor cells. RIT has been shown to be extremely effective for the treatment of some hematopoietic malignancies. However, RIT is a highly immunogenic and very toxic protein, preventing its use as an effective treatment for solid tumors, including HNSCC. In our previous studies, we produced a humanized RIT DT390-HuBiscFv806 (hDT806) targeting EGFR and demonstrated the efficacy of hDT806 in treating HNSCC and glioma. In this proposal, we will develop a novel approach to overcome the critical limitations of the current RIT application for treating HNSCC with two specific aims. Aim 1: to eliminate systemic immunogenicity and reduce RIT-induced toxicity, we will engineer synthetic Notch T cells to deliver hDT806, specifically targeting HNSCC tumor cells that overexpress EGFR. Aim 2: we will determine the efficacy of hDT806 for killing tumor cells and toxicity in immunodeficient and immunocompetent mice. The validation of scientific principles to effectively and safely deliver RIT will provide a solid rationale for a subsequent research project grant (R01) application to use RIT as a therapeutic agent in recurrent or metastatic HNSCC for which treatment options remain extremely limited.


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 = -$8,364 )
2025	2022	HOWARD UNIVERSITY	2400 6TH ST NW	WASHINGTON	DC	20059	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	000	2	2/6/2025	NON-COMPETING CONTINUATION	-$8,364
														Subtotal = -$8,364

Issue Date FY: 2022 ( Subtotal = $154,500 )
2022	2022	HOWARD UNIVERSITY	2400 6TH ST NW	WASHINGTON	DC	20059	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	000	2	5/31/2022	NON-COMPETING CONTINUATION	$154,500
														Subtotal = $154,500

Issue Date FY: 2021 ( Subtotal = $154,500 )
2021	2021	HOWARD UNIVERSITY (INC)	2400 6TH ST NW	WASHINGTON	DC	20059	DISTRICT OF COLUMBIA	USA	Oral Diseases and Disorders Research	000	1	6/25/2021	NEW	$154,500
														Subtotal = $154,500

Grand Total All Awards = $300,636

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Development of T cell-mediated targeted gene delivery of immunotoxin in HNSCC

Award Number: R03DE030227

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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