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By 2007, there were two fully human anti CTLA-4 [51] monoclonal antibodies in advanced clinical trials. Ipilimumab, which is an IgG1 isotype, and tremelimumab (from Pfizer) which is an IgG2 isotype. [52] [53]
Tremelimumab, sold under the brand name Imjudo, is a fully human monoclonal antibody used for the treatment of hepatocellular carcinoma (a type of liver cancer). [7] [8] 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 body’s natural defenses).
CTLA-4 is a member of the immunoglobulin superfamily that is expressed by activated T cells and transmits an inhibitory signal to T cells.CTLA-4 is homologous to the T-cell co-stimulatory protein, CD28, and both molecules bind to CD80 and CD86, also called B7-1 and B7-2 respectively, on antigen-presenting cells.
Cadonilimab is a PD-1/CTLA-4 bispecific monoclonal antibody [1] [2] developed to treat a variety of solid cancer types. In June, 2022 it was approved in China "for use in patients with relapsed or metastatic cervical cancer (r/mCC) who have progressed on or after platinum-based chemotherapy". [3]
The first checkpoint antibody approved by the FDA was ipilimumab, approved in 2011 for treatment of melanoma. [2] It blocks the immune checkpoint molecule CTLA-4. Clinical trials have also shown some benefits of anti-CTLA-4 therapy on lung cancer or pancreatic cancer, specifically in combination with other drugs. [12] [13]
Most of them are targeting immune checkpoints (CTLA-4, PD1/PD-L1, ...). [4] The only oligoclonal antibody treatment against immune checkpoint currently approved is the cocktail of nivolumab (anti-PD1 antibody) and ipilimumab (anti-CTLA-4 antibody). It is used to treat melanomas, [8] low-risk renal cancer and colorectal cancer. [4]
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