GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE303nnn/GSE303863/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE303863GEOGSEfalseCD28 co-stimulatory domain enhances efficacy of CER T cell therapy compared to 4-1BB in an ovarian cancer mouse modelOvarian 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.2026/05/14GSE303863GSM9137086GSM9137085GSM9137088GSM9137087GSM9137089GSM9137091GSM9137080GSM9137090GSM9137082GSM9137081GSM9137084GSM913708324247303863Mus musculus[41813798]