Ask about this productRelated genes to: PSCA protein
- Gene:
- PSCA NIH gene
- Name:
- prostate stem cell antigen
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 8q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-25
- Date modifiied:
- 2016-10-25
Related products to: PSCA protein
Related articles to: PSCA protein
- Pancreatic cancer remains one of the most lethal malignancies worldwide, with pancreatic ductal adenocarcinoma (PDAC) accounting for the majority of cases and exhibiting a persistently poor prognosis. Although chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable success in hematological malignancies, its therapeutic efficacy in pancreatic cancer remains limited. This review summarizes recent advances in CAR-T cell therapy for pancreatic cancer, with a focus on representative tumor-associated targets, including mesothelin (MSLN), claudin 18.2 (CLDN18.2), prostate stem cell antigen (PSCA), CD155, CD276, growth arrest-specific protein 6 (GAS6), and glypican-1 (GPC1), while also highlighting emerging next-generation CAR-T engineering strategies, including nanobody-based antigen recognition, cytokine-armored CAR-T cells, allogeneic CAR-NKT platforms, dual-target and logic-gated CAR systems, and innovative delivery approaches. Current preclinical and early clinical evidence suggests that several targets, particularly MSLN and CLDN18.2, show promising antitumor activity; however, durable clinical responses remain difficult to achieve. The major barriers include the dense desmoplastic stroma, highly immunosuppressive tumor microenvironment (TME), antigen heterogeneity, antigen loss, limited CAR-T persistence and expansion, T-cell exhaustion, and on-target, off-tumor toxicity. To overcome these obstacles, emerging strategies have focused on remodeling the TME, engineering armored or dual-target CAR-T cells, developing logic-gated CAR systems, improving CAR-T persistence, and optimizing delivery approaches through nanomaterials, oncolytic viruses, in situ CAR-T generation, alternative immune-cell carriers, and locoregional administration. Overall, CAR-T therapy for pancreatic cancer is progressing from preclinical exploration toward clinical translation. Future success will likely depend on rational target selection, multi-dimensional TME modulation, advanced CAR engineering, precision delivery, and biomarker-guided patient stratification. - Source: PubMed
Publication date: 2026/08/07
Xiao Ru-YanJiang Ye-FanZhao WeiWang Qing-QingHuang You-QingLi Xin-YuXiao Yu-JieYao HaoDai Rui-Wu - Infection susceptibility and systemic infection severity arise from distinct tissue barriers and host-response compartments, but plasma-protein genetic studies often treat infection as a broad phenotype. We aimed to define a site-resolved host plasma-protein architecture of infection susceptibility across urinary, lower-respiratory, systemic, and skin/soft-tissue infection outcomes. We performed proteome-wide two-sample cis-protein quantitative trait locus (cis-pQTL) Mendelian randomization (MR) using UK Biobank Pharma Proteomics Project (UKB-PPP) instruments and registry-derived FinnGen R13 infection endpoints. Prioritized protein-outcome pairs underwent regional colocalization, prior-sensitivity analysis, Steiger-like directionality sensitivity, Finnish and broader European reference-panel linkage disequilibrium (LD) assessment, candidate-level deCODE pQTL-source follow-up where feasible, and druggability and safety-domain annotation. Across 18,766 harmonized tests, evidence was strongly site-resolved. PSCA emerged as the principal novel cystitis-specific candidate (OR 0.977, 95% CI 0.967-0.987), with strong colocalization and high Finnish reference-panel linkage disequilibrium between the MR instrument and the top colocalization single-nucleotide polymorphism (SNP) (r = 0.980). UMOD anchored urinary host-defense coherence. APOE showed strong evidence for the registry-derived implicit sepsis endpoint but was interpreted as a pleiotropy-prone broad host-response or severity-associated locus. TNFSF8 retained a robust pneumonia MR signal, but colocalization was moderate (PP.H4 = 0.544) and became weak under stringent priors (PP.H4 = 0.107), despite high-LD deCODE proxy-instrument follow-up. Skin/soft-tissue infection lacked a convergent lead. This study supports a site-resolved architecture of genetically anchored plasma-protein candidates for infection susceptibility. PSCA and UMOD define complementary urinary signals, whereas APOE and TNFSF8 require cautious interpretation as broad host-response and lower-respiratory follow-up hypotheses rather than established therapeutic targets. - Source: PubMed
Publication date: 2026/07/29
Ji ShanLi Tongzeng - CD28 is a costimulatory component of several second-generation chimeric antigen receptor (CAR)-T cells, providing signals essential for T cell proliferation, survival, and cytokine secretion. However, the specific contribution of individual CD28 intracellular motifs to CAR-T cell function remains incompletely understood. Here, we identify tyrosine 218 (Y218) in the CD28 cytoplasmic domain as a critical regulatory site and demonstrate that its phosphorylation is essential for optimal CAR-T cell activity. Using a 218F mutant, we show that loss of Y218 phosphorylation leads to impaired IL-2 production and abrogates antitumor efficacy. Transcriptomic profiling of 218F CAR-T cells revealed increased expression of IL-17A, IL-17F, and related cytokines, suggesting a shift toward a pro-inflammatory Th17-like phenotype that may contribute to dysfunction. Mechanistically, we demonstrate that the interleukin-2-inducible T cell kinase, ITK, mediates Y218 phosphorylation. To translate this mechanistic insight into improving CAR design, we engineered a novel CAR incorporating a synthetic ITK-binding motif (PYRP). This novel design enhances ITK recruitment, increases Y218 phosphorylation, boosts IL-2 secretion, and improves antitumor efficacy in vivo. Our findings underscore the functional relevance of Y218 phosphorylation in modulating CAR-T cell fate and reveal a strategy to fine-tune CAR signaling through targeted kinase recruitment to enhance therapeutic efficacy. - Source: PubMed
Publication date: 2026/08/25
Martinez-Planes ElenaRamello Maria CeciliaFontela Miguel GShokri Mohammad-RezaTran Timothy HDarville LanciaKoomen John MKim YoungchulAbate-Daga Daniel - Consensus molecular classes of urothelial carcinoma (UC) include basal/squamous (Ba/Sq), luminal papillary (LumP), luminal nonspecified (LumNS), luminal unstable (LumU), stroma-rich, and neuroendocrine (NE)-like. We aimed to determine the consensus molecular classifications of micropapillary (MP), plasmacytoid (PC), and sarcomatoid (SM) subtypes of bladder UC and characterize their spatial transcriptomic profiles. - Source: PubMed
Publication date: 2026/08/25
Zhao TingNawrocki ColeXiong LinjieNieman Linda TSaylor Philip JBlute Michael LMiyamoto David TTing David TDahl Douglas MWu Chin-Lee - Due to its overexpression in the tumor microenvironment of most solid malignancies, fibroblast activation protein (FAP) has emerged as an ideal target for (immuno)theranostic applications. The clinically tested UniCAR system represents a promising adapter CAR T-cell approach, in which CAR T-cell activity is regulated through the administration of target modules (TMs). Here, we report the first homodimeric FAP inhibitor (FAPI)-based TMs that enable efficient adapter CAR T-cell immunotherapy of FAP-positive tumors. The novel TMs consist of two UAMC-1110 FAPI moieties, the E5B9 UniCAR epitope, a suitable polyethylene glycol spacer to ensure epitope accessibility, and a functional group that allows for further TM functionalization for diagnostic and radiotherapeutic applications. Following the synthesis of the novel FAPI TMs, we evaluated their functionality using both in vitro and in vivo models. The FAPI TMs successfully redirect UniCAR T-cells and mediate potent lysis of FAP-positive cells in vitro and in an immunodeficient mouse model. In addition, we established a 3D heterospheroid model consisting of tumor cells expressing prostate stem cell antigen (PSCA) alongside FAP-positive stromal fibroblasts. We showed that simultaneous dual-targeting leads to enhanced UniCAR-mediated cytotoxicity. Notably, fibroblast killing is mediated by the release of PSCA from dying tumor cells and its subsequent binding to the surface of neighboring PSCA-negative fibroblasts, thereby making them susceptible to PSCA-directed targeting. Overall, our work not only summarizes the successful development of novel dimeric FAPI adapter molecules for immunotherapeutic applications in solid tumors but also provides novel insights into the targeting of PSCA-positive tumors. - Source: PubMed
Publication date: 2026/08/21
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