B7H3

Targeting ferroptosis-related pathway is a potential strategy for treatment of lung cancer (LC). Consequently, exploration of ferroptosis-related markers is important for treating LC. We collected LC clinical data and mRNA expression profiles from TCGA and GEO database. Ferroptosis-related genes (FRGs) were obtained through FerrDB database. Expression analysis was performed to obtain differentially expressed FRGs. Diagnostic and prognostic models were constructed based on FRGs by LASSO regression, univariate, and multivariate Cox regression analysis, respectively...

The intracellular delivery of cargos via cell penetrating peptides (CPPs) holds significant promise as a drug delivery vehicle, but a major issue is their lack of cell type specificity, which can lead to detrimental off-target effects. We use an ADEPT-like concept to introduce conditional and selective activation of cellular uptake by using the lysine-rich, cationic, and amphiphilic L17E peptide as a model CPP. By masking the lysine residues of the L17E peptide with enzyme-cleavable acetyl protecting groups, the delivery of the covalently conjugated fluorophore TAMRA to HeLa cells was diminished...

Encouraged by our observations of pronounced B7-H3 protein over-expression in many human solid tumors compared to healthy tissues, we focused on targeting B7-H3 with CAR T cells. We utilized a nanobody as the t B7-H3 targeting domain in our CAR construct to circumvent the stability issues associated with scFv-based domains. In efforts to expand patient access to CAR T cell therapy, we engineered our nanobody-based CAR into human Epstein-Barr Virus Specific T Cells (EBVSTs), offering a readily available off-the-shelf treatment...

The success of chimeric antigen receptor T-cell (CAR-T) therapies in the treatment of hematologic malignancies has led to the investigation of their potential in the treatment of solid tumors, including ovarian cancer. While the immunosuppressive microenvironment of ovarian cancer has been a barrier in their implementation, several early phase clinical trials are currently evaluating CAR-T cell therapies targeting mesothelin, folate receptor a, HER2, MUC16, and B7H3. Ongoing challenges include cytokine-associated and "on-target, off-tumor" toxicities, while most common adverse events include cytokine release syndrome, hemophagocytic lymphohistiocytosis/macrophage activation-like syndrome (HLH/MAS), and neurotoxicity...

Glycosylation alterations in TNBC have significant implications for tumor behavior, diagnosis, prognosis, and therapeutic strategies. Dysregulated glycosylation affects cell adhesion, signaling, immune recognition, and response to therapy in TNBC. Different types of glycosylation, including N-linked glycosylation, O-linked glycosylation, glycosphingolipid glycosylation, mucin-type glycosylation, and sialylation, play distinct roles in TNBC. The "barcoding" method based on glycosylation sites of the membrane type mannose receptor (MR) shows promise in accurately distinguishing breast cancer subtypes, including TNBC...

CAR-T-cell therapy has shown promise in treating hematological malignancies but faces challenges in treating solid tumors due to impaired T-cell function in the tumor microenvironment. To provide optimal T-cell activation, we developed a B7 homolog 3 protein (B7H3)-targeting CAR construct consisting of three activation signals: CD3ζ (signal 1), 41BB (signal 2), and the interleukin 7 receptor alpha (IL7Rα) cytoplasmic domain (signal 3). We generated B7H3 CAR-T cells with different lengths of the IL7Rα cytoplasmic domain, including the full length (IL7R-L), intermediate length (IL7R-M), and short length (IL7R-S) domains, and evaluated their functionality in vitro and in vivo...

The role of PIWI-interacting RNAs (piRNAs) in small extracellular vesicles (sEV) derived from pancreatic neuroendocrine neoplasms (PNEN) in the tumor microenvironment (TME) remains unexplored. We used multiplex immunohistochemistry (mIHC) to analyze the expression of CD68, CD276 (B7H3) and CD3 on PNEN. CD276+ tumor-associated macrophages (TAMs) were more abundant in tumor tissues than nontumor tissues and negatively correlated with T-cell infiltration. Serum sEV piRNA sequencing was performed to identify piRNAs enriched in PNEN patients...

Mortality due to malignant tumors is one of the major factors affecting the life expectancy of the global population. Therapeutic antibodies are a cutting-edge treatment method for restricting tumor growth. B7-H3 is highly expressed in tumor tissues, but rarely in normal tissues. B7-H3 is closely associated with poor prognosis in patients with tumors. B7-H3 is an important target for antitumor therapy. In this study, the fully human anti-B7H3 single-chain antibodies (scFvs) were isolated and screened from the fully human phage immune library with B7H3 as the target...

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis...

PURPOSE: Surgery impairs immune function and increases postoperative complications. B7H3, a co-stimulatory molecule, plays a crucial role in immune regulation. The present study examined the impact of B7H3 on the postoperative immune response in children with acute suppurative appendicitis (ASA) by comparing preoperative and postoperative B7H3 levels in laparoscopic surgery (LA) and open appendectomy (OA). PATIENTS AND METHODS: 198 pediatric ASA patients were enrolled...

Oncolytic viruses have emerged as a promising modality for cancer treatment due to their unique abilities to directly destroy tumor cells and modulate the tumor microenvironment. Bispecific T-cell engagers (BsAbs) have been developed to activate and redirect cytotoxic T lymphocytes, enhancing the antitumor response. To take advantage of the specific infection capacity and carrying ability of exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-1dko -B7H3nb/CD3 or HSV-1dko -B7H3nb/mCD3, carrying a B7H3nb/CD3 or B7H3nb/mCD3 BsAb that replicates and expresses BsAb in tumor cells in vitro and in vivo...

The emergence of immune escape is a significant roadblock to developing effective chimeric antigen receptor (CAR) T cell therapies against hematological malignancies, including acute myeloid leukemia (AML). Here, we demonstrate feasibility of targeting two antigens simultaneously by combining a GRP78-specific peptide antigen recognition domain with a CD123-specific scFv to generate a peptide-scFv bispecific antigen recognition domain (78.123). To achieve this, we test linkers with varying length and flexibility and perform immunophenotypic and functional characterization...

Despite surgical treatment combined with multidrug therapy having made some progress, chemotherapy resistance is the main cause of recurrence and death of gastric cancer (GC). Gastric cancer mesenchymal stem cells (GCMSCs) have been reported to be correlated with the limited efficacy of chemotherapy in GC, but the mechanism of GCMSCs regulating GC resistance needs to be further studied. The gene set enrichment analysis (GSEA) was performed to explore the glycolysis-related pathways heterogeneity across different cell subpopulations...

The CD28-B7 interaction is required to deliver a second signal necessary for T-cell activation. Additional membrane receptors of the CD28 and B7 families are also involved in immune checkpoints that positively or negatively regulate leukocyte activation, in particular T lymphocytes. BTLA is an inhibitory receptor that belongs to a third receptor family. Fish orthologs exist only for some of these genes, and the potential interactions between the corresponding ligands remain mostly unclear. In this work, we focused on the channel catfish (Ictalurus punctatus), a long-standing model for fish immunology, to analyze these co-stimulatory and co-inhibitory receptors...

Lung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings...

CD1d-restricted invariant NKT (iNKT) cells play a critical role in tumor immunity. However, the scarcity and limited persistence restricts their development and clinical application. Here, we demonstrated that iNKT cells could be efficiently expanded using modified cytokines combination from peripheral blood mononuclear cells. Introduction of IL-21 significantly increased the frequency of CD62L-positive memory-like iNKT cells. iNKT cells armoring with B7H3-targeting second generation CAR and IL-21 showed potent tumor cell killing activity...

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive tract with a low 5-year survival rate due to the lack of effective treatment methods. Although therapeutic monoclonal antibodies (mAbs) now play an important role in cancer therapy, effective targeted mAbs are still lacking for ESCC. B7-H3 is highly expressed in a variety of tumors and has emerged as a promising therapeutic target. Several mAbs against B7-H3 have advanced to clinical trials, but their development has not yet been pursued for ESCC...

CD276/B7-H3 represents a promising target for cancer therapy based on widespread overexpression in both cancer cells and tumor-associated stroma. In previous preclinical studies, CD276 antibody-drug conjugates (ADCs) exploiting a talirine-type pyrrolobenzodiazepine (PBD) payload showed potent activity against various solid tumors but with a narrow therapeutic index and dosing regimen higher than that tolerated in clinical trials using other antibody-talirine conjugates. Here, we describe the development of a modified talirine PBD-based fully human CD276 ADC, called m276-SL-PBD, that is cross-species (human/mouse) reactive and can eradicate large 500-1,000-mm3 triple-negative breast cancer xenografts at doses 10- to 40-fold lower than the maximum tolerated dose...

BACKGROUND: Bladder cancer is a common and highly heterogeneous malignant tumor with a relatively poor prognosis. Thus, personalized treatment strategies for bladder cancer are essential for improving patient outcomes. MATERIALS AND METHODS: We developed an efficient 3-dimensional in vitro organoid culture system for bladder cancer organoids (BCOs), which maintains the homology with the original patient tumors and the heterogeneity between different individuals...

BACKGROUND: Angiogenin (ANG) has been widely reported as a crucial molecular regulator in multiple malignancies. However, its role in gliomagenesis remains unclear. This study aimed to investigate the molecular and clinical characterization of ANG expression at transcriptome level and the association with glioma-related immune response. METHODS: A total of 301 glioma samples with mRNA microarray data (CGGA301) was obtained from the official website of CGGA project for yielding preliminary results, followed by validation in two independent RNAseq datasets, including TCGA with 697 samples and CGGA325 with 325 patients...