Monoclonal antibody | |
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Type | Whole antibody |
Source | Humanized |
Target | PD-1 |
Clinical data | |
Trade names | Tevimbra |
Other names | |
Routes of administration | Intravenous |
Drug class | Antineoplastic agent |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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Tislelizumab, sold under the brand name Tevimbra among others, is a humanized monoclonal antibody directed against PD-1. [6] It prevents PD-1 from binding to the ligands PD-L1 and PD-L2 (hence it is a checkpoint inhibitor). It is designed to bind less to Fc gamma receptors. [7] It is being developed by BeiGene (after a period with Celgene Corp). [8]
Tislelizumab was approved by China's National Medical Products Administration:
Adverse effects include anemia, leukopenia, thrombocytopenia, nausea, increased aspartate transaminase (AST), neutropenia, fatigue, decreased appetite, vomiting, musculoskeletal pain, constipation, hypoproteinemia and rash. [11] Fatal events such as respiratory infection or failure, and hepatic injury have been reported. [12]
Adverse events are more common when combined with chemotherapy. [13]
Phase I clinical trial from 2016 has results suggesting an elimination half-life of 11 to 17 days. [6] A 2021 structural and functional analysis suggests a t1/2 of 238 ± 32 minutes, 30- to 80-times higher than pembrolizumab and nivolumab. [14]
Phase I trials began in the US and Australia in June 2015. [15] Some early results were announced in July 2016. [16] [6]
A phase II clinical trial for urothelial cancer started in China in 2017. [7]
It has completed phase III trial for NSCLC. [17] As of April 2024 [update] , no results have been posted.
Tislelizumab "demonstrated efficacy and tolerability" in a multicenter phase III trial for advanced hepatocellular carcinoma started in January 2018. [8] [18]
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.
Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively and postoperatively.
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Treatment of lung cancer refers to the use of medical therapies, such as surgery, radiation, chemotherapy, immunotherapy, percutaneous ablation, and palliative care, alone or in combination, in an attempt to cure or lessen the adverse impact of malignant neoplasms originating in lung tissue.
TIGIT is an immune receptor present on some T cells and natural killer cells (NK). It is also identified as WUCAM and Vstm3. TIGIT could bind to CD155 (PVR) on dendritic cells (DCs), macrophages, etc. with high affinity, and also to CD112 (PVRL2) with lower affinity.
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.
Targeted molecular therapy for neuroblastoma involves treatment aimed at molecular targets that have a unique expression in this form of cancer. Neuroblastoma, the second most common pediatric malignant tumor, often involves treatment through intensive chemotherapy. A number of molecular targets have been identified for the treatment of high-risk forms of this disease. Aiming treatment in this way provides a more selective way to treat the disease, decreasing the risk for toxicities that are associated with the typical treatment regimen. Treatment using these targets can supplement or replace some of the intensive chemotherapy that is used for neuroblastoma. These molecular targets of this disease include GD2, ALK, and CD133. GD2 is a target of immunotherapy, and is the most fully developed of these treatment methods, but is also associated with toxicities. ALK has more recently been discovered, and drugs in development for this target are proving to be successful in neuroblastoma treatment. The role of CD133 in neuroblastoma has also been more recently discovered and is an effective target for treatment of this disease.
Dr. Cora Sternberg is an American medical oncologist at Weill Cornell Medicine and NewYork-Presbyterian Hospital, serving as a member of the Genitourinary (GU) Oncology Program. Dr. Sternberg facilitates the continued growth and development of clinical and translational research programs in GU malignancies. Dr. Sternberg is an internationally respected leader in the field of medical oncology and urological malignancies and a recognized expert in the area of new drug development. She is known for her seminal contributions in bladder cancer, her strong track record of sustained genito-urinary (GU) oncology leadership and collaboration in multiple practice-changing clinical trials, including novel medicines, and her current role applying her expertise in oncology and GU cancers to precision medicine to further improve outcomes for patients. Dr. Sternberg has been decidedly influential in the development of novel hormonal therapies and checkpoint inhibitors across the landscape of GU oncology as evidenced in her curriculum vitae. She is a globally respected researcher who has lectured extensively at universities and cancer symposia worldwide (>800). As Clinical Director of the Englander Institute for Precision Medicine (EIPM), Dr. Sternberg develops strategies to incorporate genomic sequencing and precision medicine throughout the Weill Cornell Medicine and NewYork-Presbyterian healthcare network, including Lower Manhattan, Brooklyn and Queens.
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cervical cancer, and certain types of breast cancer. It is administered by slow intravenous injection.
Eftilagimod alpha is a large-molecule cancer drug being developed by the clinical-stage biotechnology company Immutep. Efti is a soluble version of the immune checkpoint molecule LAG-3. It is an APC Activator used to increase an immune response to tumors, and is administered by subcutaneous injection. Efti has three intended clinical settings:
Durvalumab, sold under the brand name Imfinzi, is an FDA-approved immunotherapy for cancer, developed by Medimmune/AstraZeneca. It is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 (CD279).
Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar soft part sarcoma, but discontinued for use in triple-negative breast cancer (TNBC). It is a fully humanized, engineered monoclonal antibody of IgG1 isotype against the protein programmed cell death-ligand 1 (PD-L1).
Avelumab, sold under the brand name Bavencio, is a fully human monoclonal antibody medication for the treatment of Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma.
PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.
Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unregulated in some tumors and influence tumor cell differentiation, proliferation, angiogenesis, and cell survival. Astex Pharmaceuticals discovered the drug and licensed it to Janssen Pharmaceuticals for further development.
Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Some cancers can protect themselves from attack by stimulating immune checkpoint targets. Checkpoint therapy can block inhibitory checkpoints, restoring immune system function. The first anti-cancer drug targeting an immune checkpoint was ipilimumab, a CTLA4 blocker approved in the United States in 2011.
Cemiplimab, sold under the brand name Libtayo, is a monoclonal antibody medication for the treatment of squamous cell skin cancer. Cemiplimab belongs to a class of drugs that binds to the programmed death receptor-1 (PD-1), blocking the PD-1/PD-L1 pathway.
CKLF like MARVEL transmembrane domain-containing 6, previously termed chemokine-like factor superfamily 6, is a transmembrane protein encoded in humans by the CMTM6 gene. This gene is located in band 22.3 on the short arm of chromosome 3. CMTM6 protein belongs to the CKLF-like MARVEL transmembrane domain-containing family of proteins. This family consist of 9 member proteins: CKLF and CMTM1 through CMTM8. The CMTM family proteins are involved in autoimmune diseases, cardiovascular diseases, the male reproductive system, haematopoiesis, and cancer development. CMTM6 protein regulates immune responses to normal and abnormal cells.
BeiGene, Ltd. is a global oncology company that specializes in the development of drugs for cancer treatment. Founded in 2010 chief executive officer by John V. Oyler and Xiaodong Wang, the multinational company headquartered in Cambridge, Massachusetts has offices in North America, Europe, South America, Asia and Australia. BeiGene has developed several pharmaceuticals, including tislelizumab, a checkpoint inhibitor, and zanubrutinib, a Bruton's tyrosine kinase inhibitor.
Roy S. Herbst is an American oncologist who is the Ensign Professor of Medicine, Professor of Pharmacology, Chief of Medical Oncology, and Associate Director for Translational Research at Yale Cancer Center and Yale School of Medicine in New Haven, Connecticut.