Enoblituzumab
(Synonyms: MGA271) 目录号 : GC68334Enoblituzumab 是一种人源化 IgG1κ 单克隆抗体，可以识别人 B7-H3 蛋白 (B7 家族的免疫调节剂成员)。
Cas No.:1353485-38-7
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Enoblituzumab (MGA271) is a humanized IgG1κ monoclonal antibody recognizing human B7-H3 protein, a member of the B7 family of immune regulators[1].
Enoblituzumab interacts with B7-H3 and causes strong antibody-dependent cellular cytotoxicity (ADCC) against a wide spectrum of cancer cells[2].
Enoblituzumab (0.01 ng/mL-10 mg/mL) mediates antibody-dependent cellular cytotoxicity (ADCC) against A498 cells with cynomolgus monkey peripheral blood mononuclear cells (PBMCs)[3].
Enoblituzumab (5 mg/kg; i.v.; single dose) exhibits estimated half-life of 249 hours with a Cmax of 43 mg/mL in mice (mCD16-/-hCD16A+) that murine CD16 gene knocked out and are transgenic for human CD16A-158F[3].
Enoblituzumab (0.1-10 mg/kg; i.v.; once weekly; 5 weeks) exhibits potent antitumor activity in B7-H3-expressing xenograft mice models of renal cell and bladder carcinoma[3].
| Animal Model: | mCD16-/-hCD16A+ mice implanted with A498 renal cell carcinoma, 786-0 renal cell carcinoma, or HT-1197 bladder carcinoma cells (s.c.)[3] |
| Dosage: | 1 mg/kg, 5 mg/kg, 10 mg/kg |
| Administration: | Intravenous injection; once weekly; 5 weeks |
| Result: | Significantly inhibited tumor growth at doses of 1 mg/kg or greater with once weekly treatment. Achieved a cytostatic response at 5 or 10 mg/kg until day 52, after which the average tumor volume of the 5 mg/kg treatment group remained near predose administration levels, whereas a nonsignificant trend toward relapse exhibited in the 10 mg/kg group. |
[1]. Hińcza-Nowak K, et al. Immune Profiling of Medullary Thyroid Cancer-An Opportunity for Immunotherapy. Genes (Basel). 2021 Sep 28;12(10):1534.
[2]. Chapoval, et al. Immune Checkpoints of the B7 Family. Part 2. Representatives of the B7 Family B7-H3, B7-H4, B7-H5, B7-H6, B7-H7, and ILDR2 and Their Receptors. Russ J Bioorg Chem 45, 321-334 (2019).
[3]. Loo D, et al. Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent antitumor activity. Clin Cancer Res. 2012 Jul 15;18(14):3834-45.
| Cas No. | 1353485-38-7 | SDF | Download SDF |
| 别名 | MGA271 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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2.
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Dual checkpoint targeting of B7-H3 and PD-1 with Enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial
J Immunother Cancer 2022 Apr;10(4):e004424.PMID:35414591DOI:10.1136/jitc-2021-004424.
Background: Availability of checkpoint inhibitors has created a paradigm shift in the management of patients with solid tumors. Despite this, most patients do not respond to immunotherapy, and there is considerable interest in developing combination therapies to improve response rates and outcomes. B7-H3 (CD276) is a member of the B7 family of cell surface molecules and provides an alternative immune checkpoint molecule to therapeutically target alone or in combination with programmed cell death-1 (PD-1)-targeted therapies. Enoblituzumab, an investigational anti-B7-H3 humanized monoclonal antibody, incorporates an immunoglobulin G1 fragment crystallizable (Fc) domain that enhances Fcγ receptor-mediated antibody-dependent cellular cytotoxicity. Coordinated engagement of innate and adaptive immunity by targeting distinct members of the B7 family (B7-H3 and PD-1) is hypothesized to provide greater antitumor activity than either agent alone. Methods: In this phase I/II study, patients received intravenous Enoblituzumab (3-15 mg/kg) weekly plus intravenous pembrolizumab (2 mg/kg) every 3 weeks during dose-escalation and cohort expansion. Expansion cohorts included non-small cell lung cancer (NSCLC; checkpoint inhibitor [CPI]-naïve and post-CPI, programmed death-ligand 1 [PD-L1] <1%), head and neck squamous cell carcinoma (HNSCC; CPI-naïve), urothelial cancer (post-CPI), and melanoma (post-CPI). Disease was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 after 6 weeks and every 9 weeks thereafter. Safety and pharmacokinetic data were provided for all enrolled patients; efficacy data focused on HNSCC and NSCLC cohorts. Results: Overall, 133 patients were enrolled and received ≥1 dose of study treatment. The maximum tolerated dose of Enoblituzumab with pembrolizumab at 2 mg/kg was not reached. Intravenous Enoblituzumab (15 mg/kg) every 3 weeks plus pembrolizumab (2 mg/kg) every 3 weeks was recommended for phase II evaluation. Treatment-related adverse events occurred in 116 patients (87.2%) and were grade ≥3 in 28.6%. One treatment-related death occurred (pneumonitis). Objective responses occurred in 6 of 18 (33.3% [95% CI 13.3 to 59.0]) patients with CPI-naïve HNSCC and in 5 of 14 (35.7% [95% CI 12.8 to 64.9]) patients with CPI-naïve NSCLC. Conclusions: Checkpoint targeting with Enoblituzumab and pembrolizumab demonstrated acceptable safety and antitumor activity in patients with CPI-naïve HNSCC and NSCLC. Trial registration number: NCT02475213.
Neoadjuvant Enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial
Nat Med 2023 Apr 3.PMID:37012549DOI:10.1038/s41591-023-02284-w.
B7 homolog 3 (B7-H3; CD276), a tumor-associated antigen and possible immune checkpoint, is highly expressed in prostate cancer (PCa) and is associated with early recurrence and metastasis. Enoblituzumab is a humanized, Fc-engineered, B7-H3-targeting antibody that mediates antibody-dependent cellular cytotoxicity. In this phase 2, biomarker-rich neoadjuvant trial, 32 biological males with operable intermediate to high-risk localized PCa were enrolled to evaluate the safety, anti-tumor activity and immunogenicity of Enoblituzumab when given before prostatectomy. The coprimary outcomes were safety and undetectable prostate-specific antigen (PSA) level (PSA0) 1 year postprostatectomy, and the aim was to obtain an estimate of PSA0 with reasonable precision. The primary safety endpoint was met with no notable unexpected surgical or medical complications, or surgical delay. Overall, 12% of patients experienced grade 3 adverse events and no grade 4 events occurred. The coprimary endpoint of the PSA0 rate 1 year postprostatectomy was 66% (95% confidence interval 47-81%). The use of B7-H3-targeted immunotherapy in PCa is feasible and generally safe and preliminary data suggest potential clinical activity. The present study validates B7-H3 as a rational target for therapy development in PCa with larger studies planned. The ClinicalTrials.gov identifier is NCT02923180.
Immune Profiling of Medullary Thyroid Cancer-An Opportunity for Immunotherapy
Genes (Basel) 2021 Sep 28;12(10):1534.PMID:34680929DOI:10.3390/genes12101534.
Medullary thyroid cancer (MTC) is a rare malignancy that arises from calcitonin-producing C-cells. Curative treatment for patients with metastatic MTC is challenging. Identifying the mechanisms by which cancer cells inhibit the activity of immune cells provides an opportunity to develop new therapies that restore anticancer activity. Little is known about the immunological phenomena underlying MTC. Here, we examined the expression profile of 395 genes associated with MTC. The study included 51 patients diagnosed with MTC at a single center. Bioinformatical analysis revealed that CD276 expression in MTC cells was at least three-fold higher than that in normal tissue. 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.
Correlation of B7-H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expression-based analysis
Prostate Cancer Prostatic Dis 2017 Mar;20(1):28-35.PMID:27801901DOI:10.1038/pcan.2016.49.
Background: B7-H3 (CD276), part of the B7 superfamily of immune checkpoint molecules, has been shown to have an immunomodulatory role. Its regulation, receptor and mechanism of action remain unclear. B7-H3 protein expression correlates with prostate cancer outcomes, and humanized monoclonal antibodies (that is, Enoblituzumab) are currently being investigated for therapeutic use. Here we used genomic expression data to examine the relationship between B7-H3 mRNA expression and prostate cancer. Methods: Prostatectomy tissue from 2781 patients were profiled using the Affymetrix HuEx 1.0 ST microarray. Pairwise comparisons were used to identify significant associations between B7-H3 expression and clinicopathologic variables, and survival analyses were used to evaluate the prognostic significance of B7-H3. Pearson's correlation analyses were performed to assess the relationship of B7-H3 expression with molecular subtypes and individual transcripts. Androgen receptor (AR) occupancy at the B7-H3 locus was determined using chromatin immunoprecipitation (ChIP), and androgen-dependent expression changes in B7-H3 was evaluated by quantitative reverse transcription PCR in LNCaP cell lines. Oncomine was queried to evaluate B7-H3 expression in metastatic disease. Results: B7-H3 mRNA expression was positively associated with higher Gleason score (P<0.001), tumor stage (P<0.001), and castrate resistant metastatic disease (P<0.0001). High B7-H3 expression correlated with the development of metastasis and prostate cancer specific mortality, but this was not significant on multi-variable analysis. B7-H3 expression correlated with ERG-positive disease (r=0.99) and AR expression (r=0.36). ChIP revealed an AR-binding site upstream of B7-H3, and the presence of androgens decreased B7-H3 expression in LNCaP suggesting potential direct AR regulation. Gene set enrichment analysis demonstrated an association of B7-H3 with androgen signaling as well as immune regulatory pathways. Conclusions: Higher B7-H3 expression correlates with Gleason grade, prostate cancer stage and poor oncologic outcomes in prostatectomy cohorts. B7-H3 expression appears to be related to androgen signaling as well as the immune reactome.