Visilizumab is a humanized and non-Fc receptor (FcR)-binding IgG2 monoclonal antibody (MoAb) directed against CD3 with potential immunosuppressive activity. Visilizumab binds to invariant CD3 epsilon, one of the non-covalently-associated subunits of T-cell receptors (TCRs) on activated T cells. Firstly, it is being investigated for use as an immunosuppressive drug in patients with ulcerative colitis and Crohn's disease. Visilizumab had a tentative trade name Nuvion and it was developed by PDL BioPharma Inc. At present, the potential therapeutic effect of visilizumab has been examined in several immune system–related disorders including ulcerative colitis, Crohn's disease, renal allograft, and acute graft-versus-host disease. Visilizumab has also been radiolabelled with technetium-99m for imaging T cells.
Acute graft-versus-host disease (GVHD) is mediated by donor T cells and remains a major barrier to successful hematopoietic cell transplantation despite prophylaxis using the best currently available drug combinations. Transplantation tolerance can be facilitated by activation-induced apoptosis of peripheral T cells triggered by specific antigens. Simultaneously, more than 95% of circulating human peripheral T-cells and activated T-cells in inflamed tissues express CD3 antigen. Visilizumab (HuM291, Nuvion, Plymouth, MN) is a novel non–FcR-binding anti-CD3 monoclonal antibody (mAb) directed against the invariant CD3ε chain of the TCR. Its human IgG2 isotype confers the longest in vivo half-life among all human IgGs and reduces its ability to activate human complement or to interact with type I and III FcRs. Engineered mutations within the IgG2 Fc at amino acid residues 234 and 237 (Val→Ala) confer the inability to bind type II FcRs. Unlike the prototypic murine anti-CD3 mAbs, which induce T-cell activation by FcR binding and recruitment of antigen-presenting cells, non–FcR-binding anti-CD3 mAbs do not activate resting T cells and therefore induce less toxicity from cytokine release in vivo. Visilizumab dissociates quickly from and causes minimal internalization of the TCR. Durable expression of the TCR allows sustained signaling by visilizumab leading to apoptosis.
Fig.1 Mechanism of action of Visilizumab
Table 1. Clinical Projects of Visilizumab*
NCT ID | Status | Conditions | Lead Sponsor | Update Time |
NCT03291249 | Not yet recruiting | NASH - Nonalcoholic Steatohepatitis, NAFLD, T2DM (Type 2 Diabetes Mellitus) | Tiziana Life Sciences, PLC | September 25, 2017 |
NCT02620865 | Active, not recruiting | Metastatic Pancreatic Adenocarcinoma, Recurrent Pancreatic Carcinoma, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer | Barbara Ann Karmanos Cancer Institute | December 3, 2015 |
NCT01420874 | Active, not recruiting | Colorectal Cancer, Cancer of Pancreas, Pancreatic Neoplasm, Malignant Neoplasm of Large Intestine, Malignant Tumor of Colon, Colon Carcinoma, Cancer of Colon, Pancreatic Cancer | Barbara Ann Karmanos Cancer Institute | August 22, 2011 |
NCT01022138 | Active, not recruiting | Breast Cancer | Barbara Ann Karmanos Cancer Institute | December 1, 2009 |
NCT03269526 | Recruiting | Locally Advanced Pancreatic Adenocarcinoma, Metastatic Pancreatic Adenocarcinoma | University of Virginia | August 31, 2017 |
NCT01030861 | Active, not recruiting | Autoantibody Positive, Non-diabetic Relatives at Risk for Type 1 Diabetes, High Risk, Impaired Glucose Tolerance | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | December 14, 2009 |
NCT03406858 | Recruiting | Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Prostate Carcinoma Metastatic in the Bone, PSA Progression, Stage IV Prostate Adenocarcinoma AJCC v7 | Barbara Ann Karmanos Cancer Institute | January 23, 2018 |
NCT03146637 | Recruiting | Advanced Liver Cancer | Benhealth Biopharmaceutical (Shenzhen) Co., Ltd. | May 10, 2017 |
NCT03540199 | Recruiting | Advanced Kidney Cancer | Fuda Cancer Hospital, Guangzhou | May 30, 2018 |
NCT03554395 | Recruiting | Advanced Gastric Cancer | Fuda Cancer Hospital, Guangzhou | June 13, 2018 |
NCT03501056 | Recruiting | Advanced Lung Cancer | Fuda Cancer Hospital, Guangzhou | April 17, 2018 |
NCT03524261 | Recruiting | Advanced Breast Cancer | Fuda Cancer Hospital, Guangzhou | May 14, 2018 |
NCT03484962 | Recruiting | Advanced Liver Cancer | Fuda Cancer Hospital, Guangzhou | April 2, 2018 |
NCT03524274 | Recruiting | Advanced Colorectal Cancer | Fuda Cancer Hospital, Guangzhou | May 14, 2018 |
NCT03509298 | Recruiting | Advanced Pancreatic Cancer | Fuda Cancer Hospital, Guangzhou | April 26, 2018 |
NCT03661424 | Not yet recruiting | Breast Cancer Female, Leptomeningeal Metastases | University of Virginia | September 7, 2018 |
NCT03272334 | Recruiting | Metastatic Breast Cancer | University of Virginia | September 5, 2017 |
NCT03344250 | Recruiting | Glioblastoma, Glioblastoma Multiforme | University of Virginia | November 17, 2017 |
NCT03515551 | Recruiting | Melanoma, Advanced NSCLC, Urothelial Carcinoma, Synovial Sarcoma | Immunocore Ltd | May 3, 2018 |
NCT02651662 | Recruiting | Lymphoma | Regeneron Pharmaceuticals | January 11, 2016 |
NCT02290951 | Recruiting | Non-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia | Regeneron Pharmaceuticals | November 14, 2014 |
NCT01147016 | Active, not recruiting | Breast Cancer | Barbara Ann Karmanos Cancer Institute | June 22, 2010 |
NCT02342613 | Active, not recruiting | Hematologic Malignancies, Graft-Versus-Host Disease | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | January 21, 2015 |
NCT01883297 | Recruiting | Recurrent, Platinum Resistant High Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | University Health Network, Toronto | June 21, 2013 |
NCT03291639 | Not yet recruiting | IL-17+ CD8 T Cells in Cancer Patients | China Medical University Hospital | September 25, 2017 |
NCT03173430 | Recruiting | Multiple Myeloma | Abramson Cancer Center of the University of Pennsylvania | June 1, 2017 |
NCT02889861 | Recruiting | Malignant Melanoma | Immunocore Ltd | September 7, 2016 |
NCT02570308 | Recruiting | Uveal Melanoma | Immunocore Ltd | October 7, 2015 |
NCT02497898 | Not yet recruiting | Lymphoma, Non-Hodgkin | The First People's Hospital of Changzhou | July 15, 2015 |
NCT01352286 | Active, not recruiting | Multiple Myeloma | Adaptimmune | May 11, 2011 |
NCT02103387 | Active, not recruiting | Breast Cancer | University of Miami | April 3, 2014 |
NCT03294824 | Recruiting | Allogeneic Hematopoietic Stem Cell Transplantation | Assistance Publique - Hôpitaux de Paris | September 27, 2017 |
NCT02535078 | Recruiting | Malignant Melanoma | Immunocore Ltd | August 28, 2015 |
NCT03512405 | Not yet recruiting | CD19 Positive, Philadelphia Chromosome Positive, Recurrent Acute Lymphoblastic Leukemia, Refractory Acute Lymphoblastic Leukemia | City of Hope Medical Center | April 30, 2018 |
NCT02997761 | Recruiting | Adult B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive | University of California, Davis | December 20, 2016 |
NCT02568553 | Recruiting | CD19 Positive, Mediastinal Lymphoma, Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic, Hodgkin Lymphoma, Recurrent Burkitt Lymphoma, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mediastinal Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Small Lymphocytic Lymphoma, Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between, Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma, Refractory Burkitt Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Follicular Lymphoma, Refractory Mantle Cell Lymphoma, Refractory Marginal Zone Lymphoma, Refractory Mediastinal Lymphoma, Refractory Non-Hodgkin Lymphoma, Refractory Small Lymphocytic Lymphoma | National Cancer Institute (NCI) | October 6, 2015 |
NCT02879695 | Recruiting | B Acute Lymphoblastic Leukemia,B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, CD19-Positive Neoplastic Cells Present, Mixed Phenotype Acute Leukemia, Mixed Phenotype Acute Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Recurrent B Acute Lymphoblastic Leukemia, Refractory B Acute Lymphoblastic Leukemia | National Cancer Institute (NCI) | August 26, 2016 |
NCT03478670 | Recruiting | Immunologic Deficiency Syndromes | GlaxoSmithKline | March 27, 2018 |
NCT02765126 | Recruiting | Heterologous Effects of Vaccines | Clifford Craig Medical Research Trust | May 6, 2016 |
NCT03157284 | Active, not recruiting | Atopic Dermatitis | Heinz Italia SpA | May 17, 2017 |
NCT02860559 | Not yet recruiting | Severe Combined Immunodeficiency | Taiga Biotechnologies, Inc. | August 9, 2016 |
NCT03429907 | Recruiting | Malignant Neoplasm of Breast | M.D. Anderson Cancer Center | February 12, 2018 |
NCT03135769 | Recruiting | Gestational Trophoblastic Neoplasias (GTN) | Hospices Civils de Lyon | May 1, 2017 |
NCT02143414 | Recruiting | Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, Philadelphia Chromosome Positive, Recurrent Adult Acute Lymphoblastic Leukemia, Refractory Adult Acute Lymphoblastic Leukemia, Untreated Adult Acute Lymphoblastic Leukemia | National Cancer Institute (NCI) | May 21, 2014 |
NCT01515462 | Active, not recruiting | Wiskott-Aldrich Syndrome | GlaxoSmithKline | January 24, 2012 |
NCT02003222 | Recruiting | Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative, BCR/ABL1 Fusion Protein Negative, Untreated Adult Acute Lymphoblastic Leukemia | National Cancer Institute (NCI) | December 6, 2013 |
NCT02101853 | Recruiting | B Acute Lymphoblastic Leukemia | National Cancer Institute (NCI) | April 2, 2014 |
We provide high-quality Visilizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.
Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=visilizumab
For research use only. Not intended for any clinical use.
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