Tremelimumab
Tremelimumab, sold under the brand name Imjudo, is a fully human monoclonal antibody used for the treatment of hepatocellular carcinoma. Tremelimumab is designed to attach to and block CTLA-4, a protein that controls the activity of T cells, which are part of the immune system.
The most common side effects when used in combination with durvalumab include rash, pruritus, diarrhea, abdominal pain, increased levels of liver enzymes, fever, hypothyroidism, cough, peripheral edema and increased level of lipase.
Tremelimumab was approved for medical use in the United States in October 2022, and in the European Union in February 2023.
Medical uses
Tremelimumab is indicated, in combination with durvalumab, for the treatment of adults with unresectable hepatocellular carcinoma.Tremelimumab in combination with durvalumab and platinum-based chemotherapy is indicated for the first-line treatment of adults with metastatic non-small cell lung cancer with no sensitizing epidermal growth factor receptor mutations or anaplastic lymphoma kinase positive mutations.
Mechanism of action
Tremelimumab aims to stimulate an immune system attack on tumors. Cytotoxic T lymphocytes can recognize and destroy cancer cells. However, there is also an inhibitory mechanism that interrupts this destruction. Tremelimumab turns off this inhibitory mechanism and allows CTLs to continue to destroy the cancer cells.Like ipilimumab, tremelimumab is antibody that binds to the protein CTLA-4, which is expressed on the surface of activated T lymphocytes and inhibits the killing of cancer cells. Tremelimumab blocks the binding of the antigen-presenting cell ligands B7.1 and B7.2 to CTLA-4, resulting in inhibition of B7-CTLA-4-mediated downregulation of T-cell activation; subsequently, B7.1 or B7.2 may interact with another T-cell surface receptor protein, CD28, resulting in a B7-CD28-mediated T-cell activation unopposed by B7-CTLA-4-mediated inhibition.
Unlike Ipilimumab, which is an IgG1 isotype, tremelimumab is an IgG2 isotype.
History
Previously in development by Pfizer, it is in investigation by MedImmune, a wholly owned subsidiary of AstraZeneca.Melanoma
Phase I and II clinical studies in metastatic melanoma showed some responses. However, based on early interim analysis of phase III data, Pfizer designated tremelimumab as a failure and terminated the trial in April 2008.However, within a year, the survival curves showed separation of the treatment and control groups.