Lamotrigine has multiple mechanisms of action, which give this drug its diverse anti-seizure properties as well as its novel thymoleptic and psychotropic properties. Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy and bipolar disorder. Rituximab: a review of its use in non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. doi:10.1159/000479980. -, Michaud HA, Eliaou JF, Lafont V, Bonnefoy N, Gros L. Tumor antigen-targeting monoclonal antibody-based immunotherapy: orchestrating combined strategies for the development of long-term antitumor immunity. We need some information from you before you start using the platform. As a member of the corticosteroid family, betamethasone is indicated for the treatment of several inflammatory conditions. A total of 26 patients (cohort 1, n = 1; cohorts 2 and 3, n = 25) discontinued treatment before completing five infusions. Cetuximab is an epidermal growth factor receptor inhibitor used for the treatment of metastatic colorectal cancer and head and neck cancer. Research shows that lamotrigine’s clinical profile is the result of distinct and overlapping mechanisms that contribute to each of its pharmacological actions. It is taken by mouth. As topical monotherapy, betamethasone is indicated to relieve pruritic and inflammatory symptoms of corticosteroid-responsive-dermatoses. This study will also evaluate efficacy, safety and tolerability of zolbetuximab, as well as its effects on quality of life. To gain full access to the content and functionality of the AdisInsight database try one of the following. See access & resources . (c) Specific lysis of CLDN18.2-expressing cell lines (left panel, endogenous; right panel, transduced) with negative control (MIA PaCa-2) by zolbetuximab-induced ADCC. See this image and copyright information in PMC. Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases. IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. For epilepsy it is used for both focal seizures and generalized seizures. Zolbetuximab is not an approved product by the U.S. FDA and/or any other regulatory authorities in other countries for any indication. -, Shan D, Ledbetter JA, Press OW. BxPC-3~ CLDN18.2 xenograft tumors were inoculated by SC injection of 8.5 × 10, Zolbetuximab alone and in combination with gemcitabine prevents lung metastasis formation in IV mouse xenograft models. Contact your organization’s admin about adding this content to your AdisInsight subscription. Cell Mol Life Sci. (d) Zolbetuximab-induced ADCC EC, Zolbetuximab alone and in combination with gemcitabine exhibits in vivo antitumor activity in mouse xenograft models. has a subscription A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. In this study, the mechanism of action and antitumor activity of zolbetuximab were investigated using nonclinical PC models. The purpose of this study is to evaluate the efficacy of zolbetuximab plus capecitabine and oxaliplatin (CAPOX) compared with placebo plus CAPOX (as first-line treatment) as measured by Progression Free Survival (PFS). 2000;48(12):673–683. Rohde C, Yamaguchi R, Mukhina S, Sahin U, Itoh K, Türeci Ö. Jpn J Clin Oncol. Your purchase entitles you to full access to the information contained in our drug profile at the time of purchase. Zolbetuximab (formerly IMAB362) is a chimeric mAb that mediates specific killing of CLDN18.2+ cancer cells through immune effector mechanisms; single-agent activity has been reported in G/GEJ cancer. Data are depicted as zolbetuximab molecules bound per cell. Full Title A Phase 2, Open-Label, Randomized Study to Assess the Antitumor Activity and Safety of Zolbetuximab (IMAB362) in Combination with Nab-Paclitaxel and Gemcitabine (Nab-P+GEM) as First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma Purpose The purpose of this study is to assess the safety of the investigational drug zolbetuximab … Common side effects include nausea, vomiting, dizziness, … to this content. If your organization The results presented here validate CLDN18.2 as a targetable biomarker in PC and support extension of the clinical development of zolbetuximab to patients with CLDN18.2-expressing PC. doi:10.4161/21624011.2014.955684. Full Title A Phase 3, Global, Multi-Center, Double-Blind, Randomized, Efficacy Study of Zolbetuximab (IMAB362) Plus mFOLFOX6 Compared with Placebo Plus mFOLFOX6 as First-line Treatment of Subjects with Claudin (CLDN)18.2-Positive, HER2- Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (WIRB) Purpose The chemotherapy … Transfus Med Hemother. In ex vivo systems using immune effector cells and serum from healthy donors, zolbetuximab Keywords: Rituximab, the humanized chimeric anti-CD20 monoclonal antibody, represents a powerful tool for treating B-cell malignancies and is licensed for the treatment of relapsed or chemorefractory low-grade or follicular non-Hodgkin's lymphoma (NHL). Zolbetuximab induces cytotoxicity against human…, Zolbetuximab induces cytotoxicity against human PC cells. The chemotherapeutic agent gemcitabine upregulated CLDN18.2 expression in cultured human PC cells and enhanced zolbetuximab-induced ADCC. -. - privacy policy. Comparison of Claudin 18.2 expression in primary tumors and lymph node metastases in Japanese patients with gastric adenocarcinoma. -, de Weers M, Tai YT, van der Veer MS, Bakker JM, Vink T, Jacobs DCH, Oomen LA, Peipp M, Valerius T, Slootstra JW, et al. 2012;12(4):278–287. (a) Binding dynamics of zolbetuximab (FITC-conjugated)…, Zolbetuximab alone and in combination with gemcitabine exhibits in vivo antitumor activity in…, Zolbetuximab alone and in combination with gemcitabine prevents lung metastasis formation in IV…, National Library of Medicine Unable to load your collection due to an error, Unable to load your delegates due to an error, Zolbetuximab induces cytotoxicity against human PC cells. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action … Zolbetuximab bound specifically and with strong affinity to human PC cells that expressed CLDN18.2 on the cell surface. In mouse xenograft tumors derived from human PC cell lines, including gemcitabine-refractory ones, zolbetuximab slowed tumor growth, benefited survival, and attenuated metastases development. Next Learn about multiple myeloma. If playback doesn't begin shortly, try restarting your device. It has been used both alone and as add-on therapy in people with bipolar who have had no success with other treatments. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. IP authentication when working within your organization’s network. Gray bars represent non-PC cell lines and controls. Of these, 54 patients were eligible and four received 300 mg/m 2 zolbetuximab in cohort 1, and 50 received 600 mg/m 2 zolbetuximab in cohorts 2 and 3. The precise mechanism of action of ESK in MDD is unknown, but the prevailing theory is that it preferentially blocks NMDA receptors on inhibitory γ-amino-butyric acid (GABA)-ergic interneurons. mRNA was isolated from DAN-G cells (untreated, treated with Gem [1 ng/mL] or GemOx [Gem 1 ng/mL + Ox 10 ng/mL] for 2 days) or Patu 8988S cells (untreated or treated with Gem [10 ng/mL] or GemOx [Gem 10 ng/mL + Ox 100 ng/mL] for 3 days). doi:10.4049/jimmunol.1003032. How to enable JavaScript in your browser? In ex vivo systems using immune effector cells and serum from healthy donors, zolbetuximab induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), resulting in the lysis of cultured human PC cells. Please enable it to take advantage of the complete set of features! If you opt-out your email will still be collected for registration purposes. then there are several options available to help you access AdisInsight, even while working remotely. Careers. The study drug (zolbetuximab) targets a gastric cancer specific protein named CLDN18.2 to help treat gastric cancer. Zolbetuximab bound specifically and with strong affinity to human PC cells that expressed CLDN18.2 on the cell surface. (e) Effect of treatment with Gem or GemOx on CLDN18 protein expression. Patients will be assigned to one of two groups by chance and given either: - zolbetuximab with mFOLFOX6; or - a placebo with mFOLFOX6 A placebo is a treatment that looks like the experimental medicine, but contains no medicine. 2019 Sep 1;30(9):1487-1495. doi: 10.1093/annonc/mdz199. The . Clipboard, Search History, and several other advanced features are temporarily unavailable. Expression levels are depicted relative to the housekeeping gene HPRT. Exact mass: 147014.3881. 2019 Dec;76(23):4663-4672. doi: 10.1007/s00018-019-03238-7. Lysates of SKBR-3 cells were used as negative control, whereas lysates of HEK293 cells stably transfected with CLDN18.2 (HEK293-p740) were used as positive control. Epub 2019 Jul 23. Another possible mechanism of acquired resistance to trastuzumab is likely due to co-existing. It does not require or replace the individual login accounts that many of you use to save searches and create email alerts. Highly expressed Claudin18.2 as a potential therapeutic target in advanced gastric signet-ring cell carcinoma (SRCC). CLDN18 protein expression was analyzed in total cell lysates of untreated, Gem- (1 ng/mL) or GemOx- (Gem 10 ng/mL + Ox 100 ng/mL) treated DAN-G, or Patu 8988S cells by Western blot and detected with the Zymed C-term polyclonal antibody. This study will also evaluate other anti-tumor effects, tumor markers and pharmacokinetics (PK) of zolbetuximab, Nab-P and GEM. (f) Influence of Gem, and 5-FU on surface expression of CLDN18.2 in Patu 8988S pancreatic cancer cells. Zolbetuximab bound specifically and with strong affinity to human PC cells that expressed CLDN18.2 on the cell surface. Please refer to our, Antineoplastics; Immunotherapies; Monoclonal antibodies, Antibody-dependent cell cytotoxicity; Claudin 18 protein inhibitors; Immunologic cytotoxicity, Yes Bethesda, MD 20894, Copyright Zolbetuximab attaches itself to Claudin 18.2 on the cancer cells causing cancer cell death. This site needs JavaScript to work properly. [L11991,L10782,L11997] Betamethasone can be used topically in combination with a vitamin D analog such as calcipotriene to … Cancer Immunol Immunother. The number of times you access AdisInsight, the number of searches you performed, and the number of profiles you viewed will be provided to your organization both in aggregate with other users and individually by your email address. Data are (a) mean of two or (b) mean ± SD of 3–5 independent donors per cell line. Final gross price and currency may vary according to local VAT and billing address. Online ahead of print. Federated access using single sign-on credentials. Onset of action ~1 hour: Elimination half-life: Adults: 3–7 hours Infants: 65–130 hours: Duration of action: 3–4 hours: Excretion: Urine (100%) Identifiers By accessing or using the AdisInsight platform you agree to the terms of use. click “show more below” to view selected important safety information, including boxed warning, and for link to prescribing information. 2017;44(5):327–336. COVID-19 is an emerging, rapidly evolving situation. Ann Oncol. For further information on how we protect and process your personal information, please refer to our A monoclonal antibody, zolbetuximab (formerly known as IMAB362), has been generated against CLDN18.2. Zolbetuximab has been investigated in 4 clinical trials, of which 4 are open and 0 are closed. 2020 Dec;11(6):1431-1439. doi: 10.21037/jgo-20-344. Drugs. Your email address will not be shared without your permission. ADCC; Claudin 18.2; IMAB362; antibody-dependent cellular cytotoxicity; complement-dependent cytotoxicity; immunotherapy; monoclonal antibody; pancreatic cancer; targeted therapy; zolbetuximab. In healthy tissue, the tight junction protein Claudin 18.2 (CLDN18.2) is present only in the gastric mucosa. This study was supported by Ganymed Pharmaceuticals GmbH (formerly Ganymed Pharmaceuticals AG), a wholly owned subsidiary of Astellas Pharma, Inc. Would you like email updates of new search results? (a) Binding dynamics of zolbetuximab (FITC-conjugated) to cell-surface CLDN18.2 on human PC cells by flow cytometry. BxPC-3 (e) and BxPC-3 (a) represent BxPC-3 cell lines from ECACC and ATCC, respectively. The unique mechanism of action (MOA) of Oxbryta directly inhibits the root cause of sickling in SCD 1,2. In this study, the mechanism of action and antitumor activity of zolbetuximab were investigated using nonclinical PC models. MECHANISM OF ACTION. Between 3 September 2010, and 24 September 2012, 268 patients were screened. 2011;186(3):1840–1848. Zolbetuximab (genetical recombination) (JAN) Formula: C6534H10066N1726O2056S44. This study is testing an experimental medicine called zolbetuximab (IMAB362). Histogram shows CLDN18.2 expression on Patu 8988S cells treated for 3 days with DMSO (gray line), 10 ng/mL Gem, 500 ng/mL 5-FU, 100 ng/mL PTX, or 500 ng/mL Ox (red line).