Dacetuzumab
目录号 : GC68305Dacetuzumab (SGN-40) 是一种人源化的 IgG1，抗 CD40单克隆抗体，具有抗淋巴瘤活性。Dacetuzumab 通过免疫效应作用(抗体依赖性细胞毒性和吞噬作用[ADCC/ADCP]) 杀死肿瘤细胞。Dacetuzumab ((SGN-40) 可用于多发性骨髓瘤研究。
Cas No.:880486-59-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- Datasheet
Dacetuzumab (SGN-40) is a humanized IgG1, anti-CD40 monoclonal antibody with anti-lymphoma activity. Dacetuzumab kills tumor cells via immune effector functions (antibody-dependent cellular cytotoxicity and phagocytosis [ADCC/ADCP]). Dacetuzumab ((SGN-40) can be used for multiple myeloma research[1].
[1]. Mohamad Hussein, et al. A phase I multidose study of dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma. Haematologica. 2010 May;95(5):845-8.
| Cas No. | 880486-59-9 | SDF | Download SDF |
| 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
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每只动物给药体积 | ul | |
动物数量 | 只 |
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2.
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Updating targets for natural killer/T-cell lymphoma immunotherapy
Cancer Biol Med 2021 Feb 15;18(1):52-62.PMID:33628584DOI:10.20892/j.issn.2095-3941.2020.0400.
Natural killer/T-cell lymphoma (NKTCL) is a highly invasive subtype of non-Hodgkin lymphoma, typically positive for cytoplasmic CD3, CD56, cytotoxic markers, including granzyme B and TIA1, and Epstein-Barr virus (EBV). The current treatment methods for NKTCL are associated with several drawbacks. For example, chemotherapy can lead to drug resistance, while treatment with radiotherapy alone is inadequate and results in frequent relapses. Moreover, hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts. In recent years, immunotherapy has shown good clinical results and has become a hot spot in cancer research. Clinical activity of targeted antibodies, such as daratumumab (anti-CD38 antibody) and brentuximab vedotin (anti-CD30 antibody), have been reported in NKTCL. Additionally, Dacetuzumab and Campath-1H have demonstrated promising results. Further encouraging data have been obtained using checkpoint inhibitors. The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL. Furthermore, anti-CCR4 monoclonal antibodies (mAbs) exert cytotoxic actions on both CCR4+ tumor cells and regulatory T cells. Depletion of these cells and the long half-life of anti-CCR4 mAbs result in enhanced induction of antitumor effector T cells. The role of IL10 in NKTCL has also been investigated. It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies. Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission. Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease. The present review outlines the known immunotherapy targets for the treatment of NKTCL.
Dacetuzumab, a humanized mAb against CD40 for the treatment of hematological malignancies
Curr Opin Investig Drugs 2009 Jun;10(6):579-87.PMID:19513947doi
Dacetuzumab, a humanized mAb targeting the CD40 antigen, is in development by Seattle Genetics Inc and licensee Genentech Inc for the potential treatment of hematological malignancies. The CD40 antigen is a highly expressed cell surface transmembrane protein that is present in normal B-cells. Experiments using blocking antibodies for the CD40 ligand demonstrated that CD40 signaling may play a role in the development and maintenance of B-cell hematological malignancies and some solid tumors. In vitro, Dacetuzumab exhibited antitumor activity against several B-cell lymphoma and multiple myeloma (MM) cell lines, and induced direct apoptosis as well as the engagement of effective antibody-dependent cell-mediated cytotoxicity. In vivo, Dacetuzumab demonstrated enhanced antitumor efficacy in combination with other mAbs and chemotherapeutic agents; many of these combinations are now being tested clinically. Early clinical trials have evaluated the pharmacokinetics, safety and efficacy of Dacetuzumab monotherapy in patients with relapsed/refractory B-cell lymphomas or MM. Targeting CD40 with Dacetuzumab resulted in modest antitumor activity in B-cell lymphomas and, to a lesser extent, in MM. In particular, patients with diffuse large B-cell lymphoma responded well to Dacetuzumab; the drug is being pursued for this indication in phase II trials.
Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial
Leuk Lymphoma 2015;56(9):2569-78.PMID:25651427DOI:10.3109/10428194.2015.1007504.
Single-agent Dacetuzumab has demonstrated antitumor activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Preclinical data demonstrated improved Dacetuzumab antitumor activity in combination with rituximab, ± chemotherapy. We designed a phase 2b, double-blind, placebo-controlled trial to compare rituximab, ifosfamide, carboplatin and etoposide (R-ICE) + Dacetuzumab with R-ICE + placebo in patients with DLBCL who relapsed after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (ClinicalTrials.gov #NCT00529503). The primary endpoint was complete response (CR); additional endpoints included failure-free survival and overall survival (OS). Overall, 151 patients were randomized (75 Dacetuzumab, 76 placebo). No notable differences between arms in demographics or subsequent treatment parameters were observed. Cytopenias, cough and infection were more frequent with Dacetuzumab. Futility analysis failed to demonstrate higher CR rates with Dacetuzumab (36% Dacetuzumab, 42% placebo); consequently, enrollment was stopped. Unplanned post hoc analysis showed that patients who underwent subsequent autologous stem cell transplant experienced improvement in OS (hazard ratio = 0.195, p = 0.004), which may be explained by potential immunomodulatory effects of Dacetuzumab on antigen-presenting cells.
A phase I multidose study of Dacetuzumab (SGN-40; humanized anti-CD40 monoclonal antibody) in patients with multiple myeloma
Haematologica 2010 May;95(5):845-8.PMID:20133895DOI:10.3324/haematol.2009.008003.
This first-in-human, phase I study evaluated the safety, maximum-tolerated dose, pharmacokinetics, and antitumor activity of Dacetuzumab in 44 patients with advanced multiple myeloma. Patients received intravenous Dacetuzumab, either in 4 uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid pre-medication). An initial dose of 4 mg/kg Dacetuzumab exceeded the maximum-tolerated dose for uniform weekly dosing. Intrapatient dose escalation with steroid pre-medication appeared effective in reducing symptoms of cytokine release syndrome and the maximum-tolerated dose with this dosing schema was 12 mg/kg/week. Adverse events potentially related to Dacetuzumab included cytokine release syndrome symptoms, non-infectious ocular inflammation, and elevated hepatic enzymes. Peak Dacetuzumab blood levels increased with dose. Nine patients (20%) had a best clinical response of stable disease. The observed safety profile suggested that Dacetuzumab may be combined with other multiple myeloma therapies. Two combination trials are ongoing. Clinical trials gov identifier: NCT00079716.
Pilot study of Dacetuzumab in combination with rituximab and gemcitabine for relapsed or refractory diffuse large B-cell lymphoma
Leuk Lymphoma 2013 Feb;54(2):277-83.PMID:22775314DOI:10.3109/10428194.2012.710328.
Dacetuzumab, a CD40-targeted, humanized antibody, mediates antitumor activity through effector cell functions and direct apoptotic signal transduction. Preclinical studies demonstrated synergistic activity between Dacetuzumab, gemcitabine and rituximab against non-Hodgkin lymphoma in vivo. A phase 1b safety/efficacy study of Dacetuzumab in combination with rituximab and gemcitabine was conducted in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Patients received Dacetuzumab at doses of 8 or 12 mg/kg IV weekly with rituximab (375 mg/m(2) IV weekly in cycle 1, then every 28 days) and gemcitabine (1000 mg/m(2) IV, days 1, 8 and 15, or days 1 and 15). Thirty-three patients with a median age of 67 years were enrolled. Common adverse events (≥ 15%) were grade 1/2 cytokine release syndrome, nausea, fatigue, thrombocytopenia, headache, decreased appetite, dyspnea, neutropenia, pyrexia, anemia, diarrhea, edema, constipation and cough. Dacetuzumab-related grade 3/4 adverse events occurred infrequently. Six of 30 evaluable patients achieved a complete response (CR) and eight a partial response (PR) per investigator assessment for an overall response rate (ORR) of 47%.