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 IgG(2) 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.


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.
Camacho
Luis H
LH
Department of Research Oncology Consultants PA, 920 Frostwood, Suite 780, Houston, TX 77024, USA. lcamacho@oncologyconsultants.com
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C520704:tremelimumab