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Pilot in vivo trial with T-cell-based delivery of immunostimulatory proteins

Award Number: R21CA288900
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 05/30/2026

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Pilot in vivo trial with T-cell-based delivery of immunostimulatory proteins - PROJECT SUMMARY In this project, the investigators will explore the feasibility of using their cell-based platform for delivering immunostimulatory proteins (IS) to achieve tumor regression in an in vivo pilot. Certain immunostimulatory proteins have activity against the minimal disease in most solid tumors. However, their systemic delivery does not permit sufficient concentrations to treat advanced disease, and their excess is associated with severe toxicities. The challenge is to enable a localized dose at high concentration that can treat advanced disease without undesired side effects. The team's mission is to harness the immune system to treat solid tumors. In line with this mission, their objective in this project is to re-configure their current cell-based delivery system to synthesize calibrated amounts of immunostimulatory proteins within the tumor microenvironment (TME); and validate the antitumor effect in a high-grade serous ovarian cancer (HGSOC) mouse model. The feasibility of the proposed experiments is supported by our previous publications and new preliminary data. Of particular relevance to the present application is the localized expression of the immunostimulatory protein, which others have shown to exert antitumor effects but is also toxic when delivered systemically. The team has already modified tumor cells for reporting the activity of their cell-based delivery system in vitro and developed an animal model with these tumor cells to assess the efficacy in vivo. The rationale is that the cell-based delivery platform will enable high, TME-localized doses of the immunostimulatory protein, proportionate to the tumor burden. The team plans to pursue this project in two aims: 1) Scale up the cells engineered to produce the immunostimulatory protein upon engaging HGSOC cells; and 2) Demonstrate function in an HGSOC mouse model. This project is significant because it will A) enable a strategy for site-specific delivery of high doses of immunostimulatory proteins to target high tumor burden, and B) result in a process that can be scaled up during preclinical studies in immunocompetent mice, as well as additional IND-enabling studies in compliance with cGMP protocols. We believe this project is innovative and a substantive departure from the status quo because instead of attempting to improve immunostimulatory protein bioavailability by exogenous delivery or by inducing endogenous expression that is only effective against the minimal disease, we will use our cell- based technology for enhancing immunostimulatory protein delivery to the TME. This will enable sufficient local immunostimulatory protein concentrations to treat advanced disease.


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 = $346,499 )
2025	2025	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Cancer Detection and Diagnosis Research	002	2	5/22/2025	NON-COMPETING CONTINUATION	$34,650
2025	2025	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Cancer Detection and Diagnosis Research	001	2	4/22/2025	NON-COMPETING CONTINUATION	$311,849
2025	2024	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Cancer Detection and Diagnosis Research	000	1	1/27/2025	NEW	$0
														Subtotal = $346,499

Issue Date FY: 2024 ( Subtotal = $293,028 )
2024	2024	SRI INTERNATIONAL	333 RAVENSWOOD AVE	MENLO PARK	CA	94025	SAN MATEO	USA	Cancer Detection and Diagnosis Research	000	1	4/2/2024	NEW	$293,028
														Subtotal = $293,028

Grand Total All Awards = $639,527

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Pilot in vivo trial with T-cell-based delivery of immunostimulatory proteins

Award Number: R21CA288900

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 05/30/2026

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