CD276 overexpression

Overexpression of B7H3, B7H4, PD-1, PD-L1, PD-L2, CD70, and Galectin-3 on tumors is significantly associated with unfavorable clinicopathological characteristics and poor prognostic factors. Hence, these immune checkpoints can serve as predictive biomarkers for prognosis and the clinicopathological features of colorectal cancer because this is essential to identify patients suitable for anticancer therapy with immune checkpoint inhibitors.

Moreover, CARs with the binders exhibited higher surface expression and greater resistance to degradation, as indicated by bulk and single-cell transcriptional profiling of the cells. The de novo design of binding domains for specific tumour antigens may potentiate the antitumour efficacy of CAR T cell therapies for other solid cancers.

Our findings characterize CD276 as promising target and preclinically document the therapeutic potential of CC-3 for BC treatment, providing a strong rationale for evaluation of CC-3 in BC patients in a clinical trial for which the recruitment has recently started.

Elevated B7H3 expression is associated with reduced oCR rates in LARC, highlighting its potential role as a prognostic biomarker. Further studies with larger cohorts are warranted to validate these findings and explore B7H3-targeted therapies as a treatment strategy for LARC.

Collectively, these results indicated that [89Zr]Zr-DFO-hu4G4 was successfully fabricated and applied in B7-H3-targeted tumor PET/CT imaging, which showed excellent imaging quality and tumor detection efficacy in tumor-bearing mice. It is a promising imaging agent for identifying tumors that overexpress B7-H3 for future clinical applications.

CD276 is markedly upregulated in bladder cancer and associated with severe pathological features, advanced disease, potential for metastasis, and diminished survival rates. It may promote bladder cancer development and progression by influencing extracellular matrix-related-related pathways, making it a viable diagnostic and prognostic biomarker for bladder cancer.

This study successfully elucidates the functional role of CD276 in ESCC. Our comprehensive analysis uncovers the significant role of CD276 in modulating immune surveillance mechanisms in ESCC, thereby suggesting that targeting CD276 might serve as a potential therapeutic approach for ESCC treatment.

The improved functional affinity by dimerization does not compensate the disadvantage of increased molecular size for imaging purposes.

Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

With clinical translational value, the predictive value of B7-H3 for conventional immunotherapy was detected using the Kaplan-Meier plotter tool, and the results showed that melanoma patients with high B7-H3 expression were insensitive to anti-PD-1 and anti-CTLA-4 immunotherapy. In conclusion, we first investigate the expression of B7-H3 in melanoma and its correlations with the TME features, and indicate B7-H3 as a promising therapeutic target in melanoma patients that are insensitive to conventional immunotherapy.

B7-H3 directly interacts with ENO1 in lung cancer cells. B7-H3 can promote proliferation and migration of lung cancer cells by modulating PI3K/AKT pathway via ENO1 activity.

CD276 is significant upregulation in ESCC tissues and facilitates the EMT process in ESCC cells via the TGF-β/SMAD signaling, thus promoting the progression of ESCC.

In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.

Consistently, our ELISA results verified the binding of 24F-Hu-WT and IgC1 and IgC2. Our results indicate that 24F-Hu-mut2 has significant anti-ESCC activity both in vitro and in vivo, and this monoclonal antibody may be a promising antibody against ESCC and other B7-H3 overexpressing tumors.

Vobra duo showed robust in vitro cytolytic activity against CD276 positive AML cells highlighting the need for ongoing preclinical evaluations of CD276 targeted therapies in AML. Given the established safety profile for vobra duo this provides a clear path for rapid translation to clinical use for high risk AML patients.

Our research suggests that COL10A1 promotes pancreatic adenocarcinoma tumorigenesis by regulating CD276. This study provides new insight into biomarkers and possible targets for pancreatic cancer treatment.

Additionally, multiplex immunohistochemistry was carried out to show the expression of B7H3, prostaglandin-endoperoxide synthase 2, and SREBP2 in CRC tumor tissues, which was associated with the prognosis of patients with CRC. In summary, our findings reveal a role for B7H3 in regulating ferroptosis by controlling cholesterol metabolism in CRC.

Low level of B7-H3 expression on TURBT specimen is a predictor of complete pathologic response to neoadjuvant chemotherapy in UCB.

This study presents a dual-compartment targeted B7H3 multifunctional gold conjugate system that can precisely control Dox exposure in a spatio-temporal manner without evident toxicity and suggests a general strategy for synergistic therapy against NSCLC.

Comprehensive in vitro characterization revealed that targeting the membrane-proximal epitope Q179 of the B7-H3 molecule allowed for a 100-fold reduction of CD3 affinity in our lead compound CC-3 with preserved superior tumor cell killing, efficient T cell activation, proliferation and memory formation, whereas undesired cytokine release was reduced...The trial will consist of a dose escalation part with an accelerated and a standard titration phase to determine the maximum tolerated dose followed by a dose expansion part to define the recommended phase II dose and collect first signs of efficacy. Together, we report on the straight forward development of a novel optimized bsAb from bench to first clinical evaluation that holds promise to improve treatment of CRC patients.

Our results suggest that B7-H3-CAR-T therapy combined with radiotherapy may be a promising modality in treating solid tumors.

B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.

Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.

We found that CRC cell-drived exosomal B7-H3 was uptaken by human umbilical vein endothelial cells (HUVECs) and consequently activated the AKT serine/threonine kinase 1 (AKT1) / mechanistic target of rapamycin kinase (mTOR) / vascular endothelial growth factor A (VEGFA) signaling pathway, thus augmenting the abilities of migration, invasion and tube formation of HUVECs...Our findings reveal that CRC-derived exosomal B7-H3 promotes tumor angiogenesis and metastasis by activating the AKT1/mTOR/VEGFA signaling pathway. It provides novel insights into the roles of CRC-drived exosomes in CRC progression.

We further demonstrate that the loss of B7-H3 in cancer cells has no effect on growth or migration in 2D but promotes the expansion of 3D spheroids in an IMPDH2-dependent manner. These findings provide new insights into the B7-H3 function in the metabolic homeostasis of normal and transformed lung cancer cells, and whilst this molecule remains an interesting target for immunotherapy, these findings caution against the use of anti-B7-H3 therapies in certain clinical settings.

This study suggested that B7-H3 regulated the Stat3/c-Met pathway. Taken together, our data showed that B7-H3 regulates NB progression by increasing glucose metabolism in NB.

Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

When engrafted with CT26 colon cancer cells, which stably overexpress human B7-H3 and PD-L1 while endogenous murine counterparts were knocked out, the tumor growth was inhibited certain degree by anti-B7-H3 antibody (8H9 Biosimilar, 20mpk, TGI=18.56%) treatment while inhibited significantly after the monotherapy of anti-PD-L1 (Tecentriq, 3 mpk, TGI=55.89%, p<0.001)...Analysis of tumor infiltrating lymphocytes (TILs) at the end of the efficacy study showed that the proportion of CD45+ immune cells was significantly increased in all of the treated groups. The NK cells was significantly increased and Treg cells was significantly decreased especially in the combined treatment group.ConclusionSummary, the B7-H3 and PD-L1 double humanized mouse model can be used in the pre-clinical evaluation of mono or combined immune checkpoint blockade with anti-human B7-H3 and PD-L1 therapy.

Furthermore, DHA treatment led to increased infiltration of CD8 T Lymphocytes in the xenografts as compared with that of negative controls. Taken together, our results suggest that B7-H3 but not PD-L1 is involved in the antitumor effects of DHA in NSCLC, which may be indicative of an effective B7-H3 blockade and further combination with anti-PD-L1/PD-1 immunotherapy.

Moreover, CC-3 induced efficient T cell proliferation and formation of T cell memory subsets. Together, our results emphasize the potential of CC-3, which is presently being GMP-produced to enable clinical evaluation for treatment of pancreatic, hepatic and gastric cancer.

Thus, fine-tuning of both, target and CD3 affinities as well as binding epitopes allowed for the generation of a B7-H3xCD3 bsAb with promising therapeutic activity. CC-3 is presently undergoing GMP production to enable evaluation in a clinical "first in human" study in CRC.

When engrafted with CT26 colon cancer cells, which stably overexpress human B7-H3 and PD-L1 while endogenous murine counterparts were knocked out, the tumor growth was inhibited certain degree by anti-B7-H3 antibody (8H9 Biosimilar, 20mpk, TGI=18.56%) treatment while inhibited significantly after the monotherapy of anti-PD-L1 (Tecentriq, 3 mpk, TGI=55.89%, p<0.001)...Analysis of tumor-infiltrating lymphocytes (TILs) at the end of the efficacy study showed that the proportion of CD45+ immune cells was significantly increased in all of the treated groups. The NK cells were significantly increased and the Treg cells were significantly decreased especially in the combined treatment group.Based on the above, the B7-H3 and PD-L1 double humanized mouse model is suitable for the pre-clinical evaluation of mono or combined immune checkpoint blockade with anti-human B7-H3 and PD-L1 therapy.

Epitope mapping revealed non-overlapping B7-H3 binding epitopes of 6B5 and Enoblituzumab. Taken together, these data suggest that 6B5 is a promising therapeutic anti-human B7-H3 IgG monoclonal antibody that may find clinical application in a range of cancers, including current refractory types.

These results highlight the low or absence of mRNA levels of the canonic targetable ICs in medulloblastomas. Importantly, the analysis revealed overexpression of CD24 and CD276, which can constitute prognostic biomarkers and attractive immunotherapy targets for medulloblastomas.

Next, BMSC-exos carrying miR-187 contributed to repressed cell malignant features as well as limited tumorigenicity and tumor metastasis. Collectively, this study demonstrated that BMSC-derived exosomal miR-187 restrained prostate cancer by reducing CD276/JAK3-STAT3-Slug axis.

Our data suggests that B7-H3 is overexpressed in primary BC and inhibits immune-cell infiltration. Moreover, blocking the immunomodulatory functions of B7-H3 using anti-B7H3 antibody T-1A5 enhances NK and T cell–mediated killing of BC cells.

ATG-027 can also inhibit the interaction between PD1/PD-L1 to rescue T cell activity suppression. ATG-027’s dual T cell activation function and powerful ADCC, CDC, and ADCP properties contribute to its promising anti-tumor efficacy in preclinical models.

Cd276 deletion also reversed the immunosuppression characterized by increased tumor-infiltrating lymphocytes. Conclusions Our studies provide the genetic evidence for the tumor-promoting and immunosuppressive role of B7-H3 in prostate cancer and offer insights into combinatorial strategies for immunotherapy targeting B7-H3 in CRPC harboring PTEN and TP53 defects.

Our data indicate that B7-H3 is overexpressed in AML and that an anti-B7-H3 antibody (T1-A5) not only blocks B7-H3's immunomodulatory function but also induces ADCC in AML cells in vitro and in vivo.

Our data indicate that B7-H3 is overexpressed in AML and that an anti–B7-H3 antibody (T1-A5) not only blocks B7-H3’s immunomodulatory function but also induces ADCC in AML cells in vitro and in vivo.