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.
2 months ago
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CD276 (CD276 Molecule)
The frequent overexpression of B7-H3 in CRPC compared with normal tissue and other B7 family members implicates it as a highly relevant therapeutic target in these diseases. Mechanisms driving differences in B7-H3 expression across genomic subsets warrant investigation for understanding the role of B7-H3 in cancer growth and for the clinical development of B7-H3 targeted therapies.
3 months ago
Journal • BRCA Biomarker
BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • AR (Androgen receptor) • CD276 (CD276 Molecule)
B7-H3 protein is overexpressed in PCa making it a promising target for immunotherapies. Examining human tissue samples, we showed an association of B7-H3 expression and aggressive clinical features, including lymph node spread. In vitro experiments with acute and chronic loss of B7-H3 revealed an effect on migration and invasion.
Conclusions DS-7300 continues to demonstrate evidence of durable antitumor activity in heavily pretreated pts with SCLC, sqNSCLC, and mCRPC. These data support further clinical development of DS-7300, including a Ph 2 dose-optimization study in SCLC (NCT05280470) with starting dose levels of 8 mg/kg and 12.0 mg/kg.
Material and Methods Spatial biomarkers characterization on tumor tissues samples from resected NSCLC (adenocarcinoma and squamous cell carcinoma) tumors treated with adjuvant pembrolizumab therapy...Conclusion Multiplexed spatial high-throughput analysis allowed to investigate at the molecular level several actors involved in immune modulation pathways responsible of drug resistance. These findings highlighted the relevance of investigating multiple biomarkers to obtain a comprehensive strategy for personalized immune therapy selection.
5 months ago
PD(L)-1 Biomarker • IO biomarker
CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD276 (CD276 Molecule) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • CD44 • CD27 • TIGIT (T Cell Immunoreceptor With Ig And ITIM Domains 2) • GZMB (Granzyme B) • CD86 (CD86 Molecule)
Furthermore, treatment with ChT-1A5 in combination with human NK cells significantly prolonged survival in AML patient-derived xenograft models. Our results suggest that ChT-1A5 antibody can inhibit the immunosuppressive function of B7-H3 protein as well as induce ADCC in B7-H3+ AML.
This is the first comprehensive study to elucidate the expression profile of B7-H3 in PTC. Our observations revealed that B7-H3 is a novel independent biomarker for predicting LNM and disease recurrence for PTC patients, and it thus may serve as an indicator that could be used to improve risk-adapted therapeutic strategies and a novel target for immunotherapy strategies for patients who undergo an aggressive disease course.
Notably, overexpression of LINC01123 or B7-H3 or downregulation of miR-214-3p inhibited the function of CD8T cells and promoted the progression of HNSCC. Therefore, LINC01123 acts as a miR-214-3p sponge to inhibit the activation of CD8T cells and promote the progression of HNSCC by upregulating B7-H3.
DS-7300a exerted potent antitumor activities against B7-H3-expressing tumors in in vitro and in vivo models including PDX mouse models and showed acceptable pharmacokinetic and safety profiles in nonclinical species. Therefore, DS-7300a may be effective in treating patients with B7-H3-expressing solid tumors in a clinical setting.
The Fab arms of SNIPER targeting GD2 and B7H3 each have low-to-moderate affinity. SNIPER binds with strong avidity when both arms bind to their antigens on the same cell. Stronger avidity through both arms binding results in high-tumor specificity.
This bispecific antibody also demonstrated potent antitumor activity in humanized mice xenograft models. These results revealed that the novel anti-B7-H3 × anti-CD3 bispecific antibody has the potential to be employed in treatment of B7-H3-positive solid tumors.
Both GOLM1 and B7-H3 knockdown restrained tumor growth and metastasis in immunodeficient mice and prolonged the survival rate. GOLM1 acts as an initial oncogenic driving gene by promoting ovarian cancer invasion and metastasis through modulating B7-H3 protein maturation and secretion.
The relationship between CD276 and chemotherapy resistance of HeLa cell were evaluated by cisplatin treatment...Furthermore, we verify the CD276's function on HeLa xenotransplantation mice model. These results suggest that CD276 elevates the self-renewal capacity of HeLa CSCs.
There is an interaction between B7H3 and FN (P=0.036) , and this interaction promoted cell adhesion (P<0.05) , inhibited cell apoptosis (P<0.05) , and activated the PI3K/AKT signaling pathway (P<0.05) . B7H3 interacts with FN to promote cell adhesion and may inhibit K562 cell apoptosis by activating the PI3K/AKT signaling pathway.
The expression of CD276 showed a weak but statistically significant positive correlation with tumor diameter, but we did not find a significant association between CD276 expression and other histopathological clinical factors, or the response to initial therapy. A search of published data identified the monoclonal antibody (inhibitor) enoblituzumab as a potential drug for patients diagnosed with MTC overexpressing CD276.
DS-7300 was generally well tolerated with early signs of clinical activity, including objective responses, in pts with pretreated advanced solid tumors. Expansion cohorts are currently enrolling to evaluate DS-7300 in selected tumor types.
Treatments to reduce immune evasion, as well as the use of other natural and pharmacological immune activators, should include prior pharmacological inhibition of steroidogenesis. Attempts to combine these with tumor cell proliferation inhibitors, if they do not affect cells of the immune system, may produce interesting results.
over 1 year ago
Journal • PD(L)-1 Biomarker • IO biomarker • Pan tumor
In animal models, upregulation of miR-29a slowed down the growth of subcutaneous xenotransplanted tumors and resulted in prolonged survival time. MiR-29a downregulates B7-H3 expression and accordingly inhibits colon cancer progression, invasion, and migration, indicating miR-29a and B7-H3 might represent novel molecular targets for advanced immunotherapy in colon cancer.
Inhibition of autophagy by inhibitors like leupeptin, chloroquine (CQ), and Bafilomycin A1 (Baf-A1) blocks the degradation of B7H3 in glioma cells...B7H3 and VEGFA are decreased in IDH-mutated gliomas and further reduced in 2-HG gliomas compared to 2-HG glioma sections by IHC staining. Our study demonstrates that B7H3 is preferentially overexpressed in IDH wild-type gliomas and could serve as a potential theranostic target for the precise treatment of glioma patients with wild-type IDH.
More importantly, B7-H3 inhibited DOX-induced cellular senescence of CRC cells in vivo. Therefore, targeting B7-H3 or the B7-H3/AKT/TM4SF1/SIRT1 pathway might be a new strategy for promoting cellular senescence-like growth arrest during drug treatment in CRC.
over 1 year ago
CD276 (CD276 Molecule) • IFIT3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) • TM4SF1 (Transmembrane 4 L Six Family Member 1)
B7-H3 is overexpressed in several TNBC cell lines and B7-H3-targeted CAR-T cells preferentially attack tumor cells with high B7-H3 expression. This B7-H3-targeted CAR-T therapy may provide an alternative approach for TNBC patients who have few therapeutic options.
CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.
B7-H3 expression is upregulated in CRC tissues and cell lines, and B7-H3 participates in promoting the proliferation and migration of CRC cells. Besides, B7-H3 expression is negatively regulated by miR-128 in CRC.
Taken together, B7-H3 humanized mice are a useful tool for in vivo efficacy evaluation and selection of candidate human B7-H3 antibodies for advancement to clinical trials. In addition, Biocytogen has generated B7-H3/PD-1 and B7-H3/PD-1/PD-L1 multi-gene humanized mice to evaluate B7-H3/PD-1/PD-L1 combination therapies in vivo.
Overexpression of CD276 promoted glucose metabolism in tumor and inhibited the function of CD8+ T cells. Therefore, strategies targeting CD276 might improve the response to cancer immunotherapy of ESCC patients.
We are developing therapeutics targeting B7-H3, including enoblituzumab, an Fc-engineered anti-B7-H3 monoclonal antibody, and MGC018, a duocarmycin-based B7-H3 ADC, both of which are currently being evaluated in clinical studies. B7-H3 is frequently overexpressed in SCCHN. At clinically relevant dose levels, MGC018 demonstrated potent antitumor activity in vivo toward SCCHN CDX mouse models and the majority of SCCHN PDX mouse models examined. These results support SCCHN as a potential indication that may be responsive to ADC-based treatments directed toward B7-H3.
over 1 year ago
Preclinical • PD(L)-1 Biomarker • IO biomarker
CD8 (cluster of differentiation 8) • CD276 (CD276 Molecule)
mB7-H3 is highly expressed in advanced PC, with higher expression associating with BRCA2 and ATM loss of function alterations and low intratumor TILs. B7-H3 may be an actionable target for treating this disease subset.
Moreover, we verified that B7-H3 upregulated VEGFA expression and angiogenesis by activating the NF-κB pathway. Collectively, our findings identify the B7-H3/NF-κB/VEGFA axis in promoting CRC angiogenesis, which serves as a promising approach for CRC treatment.