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Ligand-Induced Recruitment of CAR-T Cells to Colorectal Cancers

Award Number: R21CA286339
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Ligand-Induced Recruitment of CAR-T Cells to Colorectal Cancers - PROJECT SUMMARY Among the most powerful and successful new therapies to enter the cancer clinic is CAR-T cell therapy. CAR- T cell therapy has been remarkably effective for patients with certain refractory, progressive hematologic cancers, resulting in several FDA-approved CAR-T cell therapies. However, this therapy has not been successful for solid cancers, such as colorectal cancer (CRC), reflecting the need for suitable antigen targets for each disease, as well as patient, tumor, and immune factors, especially poor infiltration of solid tumors by CAR-T cells. The development of cellular therapies that can be applied to CRC without toxicity would have a remarkable impact on the landscape of solid cancer therapy. Here, we test the hypothesis that CAR-T cells can be engineered to home to CRC tumors by leveraging their endogenous chemokine milieus, increasing antitumor efficacy over conventional CAR-T cells. We have identified a chemokine + chemokine receptor axis that maintains an immunosuppressive tumor microenvironment (TME) in CRCs. Using validated human CRC models and target antigen, we will engineer CAR-T cells to express the chemokine receptor directed at this CRC chemokine and explore the safety and efficacy of this approach in mouse models. Aim 1 will define the tumor homing and efficacy of chemokine receptor-engineered CAR-T cells in vitro and in vivo using human CRC cell lines. Aim 2 will define the safety impact in mice because this approach may increase homing of CAR-T cells to not only tumors but also normal tissues, resulting in toxicity. Together, these studies will produce the necessary proof-of-concept data to develop this therapeutic approach for translation to clinical trials in patients with advanced/metastatic CRC.


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 = $182,325 )
2025	2025	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Treatment Research	001	2	6/27/2025	NON-COMPETING CONTINUATION	$18,232
2025	2025	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST STE 1	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Treatment Research	000	2	11/26/2024	NON-COMPETING CONTINUATION	$164,093
														Subtotal = $182,325

Issue Date FY: 2024 ( Subtotal = $218,790 )
2024	2024	THOMAS JEFFERSON UNIVERSITY	1020 WALNUT ST	PHILADELPHIA	PA	19107	PHILADELPHIA	USA	Cancer Treatment Research	000	1	12/15/2023	NEW	$218,790
														Subtotal = $218,790

Grand Total All Awards = $401,115

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Ligand-Induced Recruitment of CAR-T Cells to Colorectal Cancers

Award Number: R21CA286339

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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