Human CEACAM6 _CD66c Protein Vector: HEK294
- Known as:
- Human CEACAM6 _CD66c Protein Vector: HEK294
- Catalog number:
- 10012-H01H
- Product Quantity:
- 100μg
- Category:
- -
- Supplier:
- Provo
- Gene target:
- Human CEACAM6 _CD66c Protein Vector: HEK294
Related genes to: Human CEACAM6 _CD66c Protein Vector: HEK294
- Gene:
- CEACAM6 NIH gene
- Name:
- carcinoembryonic antigen related cell adhesion molecule 6
- Previous symbol:
- NCA
- Synonyms:
- CD66c
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1989-06-30
- Date modifiied:
- 2016-10-05
Related products to: Human CEACAM6 _CD66c Protein Vector: HEK294
Related articles to: Human CEACAM6 _CD66c Protein Vector: HEK294
- Antibody-drug conjugate (ADC) efficacy in solid tumors frequently fails to track with target abundance or binding affinity, reflecting delivery bottlenecks that remain difficult to quantify during lead selection. Here, we develop a discovery-to-function workflow for carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a glycosylphosphatidylinositol (GPI)-anchored antigen with context-dependent trafficking and show that intracellular delivery-related parameters can better organize ADC potency than antigen abundance or binding affinity alone in the CEACAM6 model system. Using multiplexed single-cell screening, we generated a mechanistically diverse anti-CEACAM6 antibody panel spanning CEACAM-family specificity, domain-level epitope usage, kinetic interaction modes, and uptake behavior. Three leads were humanized while preserving specificity and epitope identity and were conjugated to MMAE using a cleavable MC-VC-PAB linker with comparable drug loading across constructs. Despite target-dependent cytotoxicity, ADC potency and selectivity varied markedly by clone and cellular background and could not be consistently predicted by antigen expression or binding affinity alone. We defined a unitless normalized internalization degree (NID), a composite ranking metric derived from conventional surface binding and internalization assays, to integrate surface engagement with internalization efficiency. NID was associated with potency across CEACAM-expressing contexts and provided a delivery-integrated descriptor distinct from conventional internalized-fluorescence amount metrics. This delivery-related interpretation was supported by pHrodo-based tracking of accumulation in acidic compartments relevant to linker processing. The CEACAM6-selective lead h9738, prioritized based on NID profiling, exhibited robust, dose-dependent antitumor activity in a Capan-1 pancreatic cancer xenograft model, achieving complete responses (CRs) at higher doses. Collectively, these findings support a delivery-aware framework for CEACAM6 ADC optimization and identify NID as a practical, context-sensitive ranking metric for candidate prioritization for delivery-limited, GPI-anchored targets such as CEACAM6. - Source: PubMed
Publication date: 2026/06/17
Lim Joo-YoungHong JisuLee Su HyeonLee Seul-GiChae Byeong-HoSon Ga-HyunPark MinhoYoo Tae HyeonKim Yong-SungLee Chang-Han - : Pancreatic ductal adenocarcinoma (PDAC) exhibits high post-resection relapse and early systemic dissemination rates. The level of circulating tumor cells (CTCs) correlates with early metastatic failure, motivating CTC interception strategies. : In this hypothesis-driven review, we synthesized the contemporary evidence on PDAC staging and therapy, CTC detection (including portal versus peripheral sampling), and circulating tumor DNA (ctDNA)-based minimal residual disease (MRD), and evaluated the translational rationale for CTC-targeted adoptive immunotherapy focusing on CEACAM6 and CAR-T cells. : Prospective studies report higher portal versus peripheral CTC yields and stronger associations with relapse; tumor-informed ctDNA positivity in peri-operative and surveillance windows predicts shorter disease-free survival. CEACAM6 is overexpressed in PDAC and linked to invasion and metastasis, supporting antigen selection. However, target overexpression alone does not establish clinical suitability for adoptive cell transfer. Consequently, its therapeutic implementation must contend with assay heterogeneity, on-target/off-tumor risks, and the lack of interventional outcome data in PDAC, all of which remain key hurdles. : CTC-targeting is biologically plausible and operationally measurable in PDAC. Consequently, a CEACAM6-directed CAR-T approach is proposed as a potential strategy for the interception of minimal residual disease (MRD). Randomized and biomarker-selected trials with composite MRD-clearance endpoints (CTC < LOQ and ctDNA-negative) may be justified to validate this interventional hypothesis. - Source: PubMed
Publication date: 2026/06/05
Piejko MarcinBak KarolinaWierciak JoannaPlutecka HannaWilczynska-Zawal NataliaOsmola MalgorzataRapacz KamilKijowski JacekMensah-Glanowska PatrycjaSzczepanik AntoniSierzega Marek - Septic shock is a life-threatening syndrome characterized by immune dysregulation, oxidative injury, and high mortality. To identify candidate regulators linking immunity and ferroptosis in septic shock, we integrated expression quantitative trait loci (eQTL)-based Mendelian randomization (MR) with transcriptomic datasets from septic shock patients and controls. Differentially expressed genes overlapping with MR-prioritized genes were further evaluated using 113 machine-learning models, among which the glmBoost plus elastic net model (alpha = 0.9) showed strong discriminatory performance, with area under the curve (AUC) values of 0.999 in GSE26378, 0.980 in GSE26440, and 0.987 in the meta-cohort. The final model retained four risk genes, SERPINB1, DDAH2, SLC22A4, and CEACAM6. Among them, SLC22A4/OCTN1, an ergothioneine transporter, was associated with neutrophil-related immune features and better survival-related outcomes, whereas CEACAM6 showed a distinct pattern associated with immune dysregulation. Protein-ligand docking predicted potential interactions between candidate compounds and selected target proteins. In neutrophil-based validation experiments, SLC22A4 perturbation altered inflammatory cytokine production, STING-associated signaling readouts, and ferroptosis-related markers. Additional transporter-related assays showed that SLC22A4 knockdown reduced intracellular ergothioneine accumulation and that ergothioneine supplementation partially rescued erastin-induced viability loss and lipid ROS accumulation. In a cecal ligation and puncture (CLP) model, D-carnitine hydrochloride, STING-IN-5, and Keap1-Nrf2-IN-9 reshaped inflammatory cytokine responses and were associated with partial attenuation of septic lung injury. These findings suggest that SLC22A4 may represent a candidate regulator connecting immune remodeling with ferroptosis-associated dysfunction in septic shock; however, independent cohort validation, direct in vivo target-engagement studies, and further mechanistic analyses are required before therapeutic translation. - Source: PubMed
Publication date: 2026/06/11
Liu LifengYao YongdongYe JingjingZhuang HangLi YimingHuang YanjingLiu Chunyu - (Gc) causes the sexually transmitted infection gonorrhea, an urgent public health concern. Gc infection elicits a robust neutrophil response and serum leakage, but Gc has developed specialized defenses to evade both complement and neutrophils. We recently reported that the classical complement pathway inhibitor C4b-binding protein (C4BP) binds to Gc and reduces phagocytic killing by neutrophils in a complement-independent manner. Here, we used a Chinese hamster ovary (CHO) expression system and engineered C4BP constructs to define the underlying molecular mechanisms. C4BP inhibited interactions between opacity protein (Opa)-expressing Gc and carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), receptors that drive non-opsonic phagocytosis of Gc by neutrophils. The degree of C4BP-mediated inhibition varied among CEACAMs. By using wild-type and chimeric CEACAMs, we found that C4BP was more inhibitory toward the granulocyte-restricted CEACAM3 than the ubiquitously expressed CEACAM1, which we ascribed to CEACAM3's shorter extracellular domain. C4BP also inhibited the association between Opa-expressing Gc and the GPI-anchored CEACAM6. Molecules containing C4BP domains 1 and 2 fused to IgM (C4BP-IgM) or to a hexameric IgG Fc construct (C4BP-Hexa-IgG), proteins similar in diameter and degree of multimerization to native C4BP, inhibited the association of Opa-expressing Gc with CEACAM3-CHO cells to the same degree as C4BP, while Gc-binding C4BP domains fused to dimeric Fc (C4BP-IgG) did not. C4BP-IgM, but not C4BP-IgG bearing mutations to abrogate Fc gamma receptor interactions, blocked Opa-mediated phagocytosis by primary human neutrophils. These results support a model in which C4BP occludes Opa-CEACAM interactions, which protects Gc from phagocytic killing by neutrophils. - Source: PubMed
Publication date: 2026/06/10
Broden Mary WShaughnessy JutamasMohlin FridaCardenas Amaris JBlom Anna MRam SanjayCriss Alison K - Leptomeningeal disease (LMD) is a rapidly fatal complication of systemic cancer for which sensitive diagnostic tools and informative biomarkers remain limited. Here, we introduce CSF-Seq, a method for whole-transcriptome sequencing of cell-free RNA (cfRNA) from human cerebrospinal fluid (CSF), designed to enable molecular profiling of LMD and other central nervous system (CNS) conditions. Using a prospectively collected CSF biobank, we analyzed 125 samples spanning multiple pathologies, including breast and lung LMD, glioblastoma, traumatic brain injury, and non-cancer neurological controls. Through optimized RNA extraction, library preparation, and deep sequencing, CSF-Seq generated robust and reproducible transcriptome-wide profiles despite the low abundance and fragmentation of cfRNA in CSF. CSF transcriptomes exhibited disease-specific expression, separating LMD from non-cancer controls and from non-LMD cancers, independent of CSF collection modality. Tumor-associated epithelial transcripts, including CEACAM6 and MUC1, were consistently enriched in LMD samples, whereas immune and CNS-associated transcripts were broadly detected across disease states, consistent with contributions from both tumor and non-tumor sources. Cross-site processing of matched samples demonstrated high concordance, indicating preservation of sample-specific transcriptional signatures across independent workflows. Importantly, we identified a collection method- independent LMD gene expression signature that was significantly associated with overall survival, supporting its potential prognostic relevance. Together, these findings establish CSF-Seq as a technically robust and clinically informative platform for transcriptomic biomarker discovery in CNS metastatic disease, offering a minimally invasive approach for disease characterization, risk stratification, and longitudinal monitoring in patients with LMD. - Source: PubMed
Publication date: 2026/05/26
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