When an artery is blocked, cells lack oxygen, needed to produce ATP in mitochondria. ATP is required for the maintenance of electrolyte balance, particularly through the Na/K ATPase. This leads to an ischemic cascade of intracellular changes, necrosis and apoptosis of affected cells.Cells in the area with the worst blood supply, just below the inner surface of the heart (endocardium), are most susceptible to damage. Ischemia first affects this region, the subendocardial region, and tissue begins to die within 15–30 minutes of loss of blood supply. The dead tissue is surrounded by a zone of potentially reversible ischemia that progresses to become a full-thickness transmural infarct. The initial "wave" of infarction can take place over 3–4 hours. These changes are seen on gross pathology and cannot be predicted by the presence or absence of Q waves on an ECG. The position, size and extent of an infarct depends on the affected artery, totality of the blockage, duration of the blockage, the presence of collateral blood vessels, oxygen demand, and success of interventional procedures.Tissue death and myocardial scarring alter the normal conduction pathways of the heart, and weaken affected areas. The size and location puts a person at risk of abnormal heart rhythms (arrhythmias) or heart block, aneurysm of the heart ventricles, inflammation of the heart wall following infarction, and rupture of the heart wall that can have catastrophic consequences.Injury to the myocardium also occurs during re-perfusion. This might manifest as ventricular arrhythmia.
Tebentafusp, sold under the brand name Kimmtrak, is an anti-cancer medication used to treat uveal melanoma (eye cancer).The most common side effects include cytokine release syndrome, rash, pyrexia (fever), pruritus (itching), fatigue, nausea, chills, abdominal pain, edema, hypotension, dry skin, headache, and vomiting.Tebentafusp is a bispecific gp100 peptide-HLA-directed CD3 T cell engager. It was approved for medical use in the United States in January 2022. Medical uses
Tebentafusp is indicated for HLA-A*02:01-positive adults with unresectable or metastatic uveal melanoma. History
Efficacy was evaluated in IMCgp100-202 (NCT03070392), a randomized, open-label, multicenter trial of 378 participants with metastatic uveal melanoma. Participants were required to be HLA-A*02:01 genotype positive identified by a central assay. Participants were excluded if prior systemic therapy or localized liver-directed therapy were administered. Prior surgical resection of oligometastatic disease was permitted. Participants with clinically significant cardiac disease or symptomatic, untreated brain metastases were excluded.The U.S. Food and Drug Administration (FDA) granted Immunocores application for tebentafusp priority review, breakthrough therapy, and orphan drug designations. Society and culture
Legal status
On 24 February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kimmtrak, intended for the treatment of uveal melanoma. The applicant for this medicinal product is Immunocore Ireland Limited. Tebentafusp was approved for medical use in the European Union in April 2022. References
External links
"Tebentafusp". Drug Information Portal. U.S. National Library of Medicine.