Novel therapies targeting the immune system: CTLA4 blockade with tremelimumab (CP-675,206), a fully human monoclonal antibody

Background: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is an activation-induced transmembrane receptor. Binding of CTLA4 to its natural ligands downregulates T-cell activation. Tremelimumab, a fully human IgG2 monoclonal antibody binds CTLA4 and prevents ligand interaction resulting in enhanced cellular immunity. Objective: To provide a comprehensive overview of the preclinical and clinical studies conducted during the development of tremelimumab. Methods: Data with tremelimumab from all relevant preclinical studies and clinical trials completed at the time of publication and submitted to scientific meetings or published in peer-reviewed journals were collected and analysed. Salient clinical aspects observed during its early development were also included. Results/conclusions: CTLA4 blockade with tremelimumab at 15 mg/kg every 3 months has demonstrated substantial antitumor activity and an overall safe profile in patients with advanced melanoma. Phase III studies in melanoma and earlier stages of clinical development in colorectal, pancreatic, breast, and non-small cell lung carcinomas are ongoing.