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CD28 co-stimulatory domain enhances efficacy of CER T cell therapy compared to 4-1BB in an ovarian cancer mouse model

ABSTRACT: Ovarian cancer remains a significant cause of cancer-related mortality, with epithelial ovarian cancer (EOC) being the most common subtype. Despite advances in treatment, the 5-year survival rate for late-stage EOC remains low due to factors such as tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). This study investigates the therapeutic potential of chimeric endocrine receptor (CER) T cells engineered to express follicle stimulating hormone (FSH) in a syngeneic mouse model of EOC expressing follicle stimulating hormone receptor (ID8-FSHR). We compared two different co-stimulatory domains—CD28ζ and 4-1BBζ—in FSH-CER T cells and found that FSH-CD28ζ CER T cells exhibited enhanced cytotoxicity, proliferation, and cytokine secretion in vitro and in vivo. In the ID8-FSHR mouse model, FSH-28ζ CER T cells significantly reduced tumor burden and extended survival compared to FSH-hBBζ and control CER T cells. However, the therapeutic efficacy was compromised by T cell exhaustion, with all FSH-CER T cells expressing high levels of exhaustion markers after 7 days. In summary, incorporating a CD28ζ costimulatory domain enhances the efficacy of FSH-CER T cells, highlighting their therapeutic potential in ovarian cancer and supporting the development of strategies to mitigate immune exhaustion.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Ascites

SUBMITTER: Min Ma

LAB HEAD: Jun Qu

PROVIDER: PXD066774 | Pride | 2026-04-27

REPOSITORIES: Pride

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			Action	DRS
	20240712_Ascities_10_DIA_4Th_5ms_CAcol228_CA100trap_V3to35_4to35B_50min_1ul.raw	Raw
	20240712_Ascities_1_DIA_4Th_5ms_CAcol228_CA100trap_V3to35_4to35B_50min_1ul.raw	Raw
	20240712_Ascities_2_DIA_4Th_5ms_CAcol228_CA100trap_V3to35_4to35B_50min_1ul.raw	Raw
	20240712_Ascities_3_DIA_4Th_5ms_CAcol228_CA100trap_V3to35_4to35B_50min_1ul.raw	Raw
	20240712_Ascities_4_DIA_4Th_5ms_CAcol228_CA100trap_V3to35_4to35B_50min_1ul.raw	Raw

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CD28 co-stimulatory domain enhances efficacy of CER T cell therapy compared to 4-1BB in an ovarian cancer mouse model.

Beatty Nolan J NJ Ma Min M Goala Payal P McSain Shannon S Lee Sae Bom SB Boucher Justin C JC Stone Meredith L ML Kang Yun Pyo YP Cortes-Gomez Eduardo E Wang Jianmin J Qu Jun J Davila Marco L ML

Scientific reports 20260311 1

PMID: 41813798

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