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Revitalizing aged chimeric antigen receptor (CAR) T cells with the anti-inflammatory cytokine IL-37

Award Number: F31AI200254
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/01/2027
PERIOD OF PERFORMANCE END DATE: 12/31/2027

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Revitalizing aged chimeric antigen receptor (CAR) T cells with the anti-inflammatory cytokine IL-37 - PROJECT SUMMARY: Despite promising advances in CD19-targeted CAR T cell therapy of acute B-lineage leukemias, a large subset of patients over the age of 65 do not achieve long-term benefits due to lack of durable response. As current FDA-approved CAR T cell products are autologous, aging-associated chronic inflammation and the consequent decline of immune cell function are thought to contribute to higher rates of relapse in this subset of patients. Aging is associated with chronic inflammation and compromised immunity. The term “inflammaging” was introduced to describe the chronic pro-inflammatory state observed in older individuals in the absence of an acute immune response. IL-37 is an anti-inflammatory cytokine in the IL-1 family that is expressed by a variety of epithelial, endothelial, and immune cells in response to inflammatory stimuli. IL-37 functions extracellularly through binding of membrane-bound receptors to inhibit intracellular activation signaling pathways and reduce the production of proinflammatory cytokines. Studies have shown that gene expression of IL-37 significantly declines with age in human cells, but recombinant supplementation of the cytokine to aged T cells leads to the reduction of aging-associated inflammatory signaling. The objective of this proposal is to characterize the phenotypic and functional differences of IL-37-secreting CAR T cells in the context of chronic inflammation in patients over the age of 65 with B cell leukemias. I hypothesize that constitutive expression of IL-37 by aged CAR T cells will reinvigorate and protect adoptively transferred T cells from the immunosuppressive inflammaged microenvironment. We will test this hypothesis by determining the phenotype and function of aged patient- derived CAR T cells modified to co-express IL-37 cytokine as well as characterizing IL-37-secreting CAR T cells within aged syngeneic mouse models of B cell leukemia. Our work will develop a novel CAR T cell specifically engineered for patients with advanced age experiencing age-associated chronic inflammation. Broadly, I anticipate the findings of our research to contribute to the growing understanding of aging-associated immune dysfunction in the context of cellular therapies for cancer.


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 = $50,114 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Allergy and Infectious Diseases Research	000	1	7/1/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Revitalizing aged chimeric antigen receptor (CAR) T cells with the anti-inflammatory cytokine IL-37

Award Number: F31AI200254

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/01/2027

PERIOD OF PERFORMANCE END DATE: 12/31/2027

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