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Advancing ProCAR therapy toward clinical application

Award Number: R01CA313939
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/23/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Advancing ProCAR therapy toward clinical application - PROJECT SUMMARY Synthetic biology is ushering in a new era in medicine through the engineering of living cells. This approach enables the development of engineered drug-delivery systems that can intelligently detect and adapt to different environments, offering enhanced specificity and effectiveness beyond current molecular-based methods. Although such living drugs have shown significant success, they face numerous challenges in treating solid neoplasms, including the absence of uniformly expressed specific antigens, antigen loss as a resistance mechanism, and poor infiltration along with hostile microenvironments that lead to T cell dysfunction. By designing cooperative interactions between mammalian effectors and other modalities, such as engineered probiotics, these limitations can potentially be overcome. Over the last few decades, microbiome and mechanistic studies have elucidated the remarkable ability of certain bacteria to invade and thrive in immunologically and metabolically distinct environments. Where mammalian effectors – whose activity is antigen-dependent – struggle to target and infiltrate lesions, bacteria naturally home, colonize, and remain indifferent to their antigenic profile. Harnessing advances in synthetic biology, probiotics can be engineered as beacons which direct and enhance the activity of immune cells, such as probiotic-guided ProCAR-T cells, which are guided by orthogonal antigens released from engineered probiotics. This project proposal seeks to advance the bridge between a pro- and eukaryote cooperative, cross-domain platform. Specifically, we will improve pharmacokinetics of the engineered probiotics through genetic attenuations and gene circuits as well as enable long-range ProCAR-T cell interactions through probiotic-payload production and ProCAR-T cell engineering. Because the therapeutic activity of engineered probiotics and ProCAR-T cells depends on complex interactions among the tumor, immune system, and host tissues, vertebrate animal models are required to evaluate bacterial colonization, biodistribution, safety, and antitumor efficacy in vivo. These studies cannot be adequately replicated using existing in vitro systems and thus our project will involve the use of mouse models of cancer. This work represents a fundamentally new approach to genetically engineering interactions between living medicines, combining the advantages of redirected immune cells and bacteria, and lays the foundation for next-generation engineered communities.


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 = $635,722 )
2026	2026	THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK	615 W 131ST ST	NEW YORK	NY	10027	NEW YORK	USA	Cancer Treatment Research	000	1	7/23/2026	NEW	$635,722
														Subtotal = $635,722

Grand Total All Awards = $635,722

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Advancing ProCAR therapy toward clinical application

Award Number: R01CA313939

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/23/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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