Anti-infective monoclonal antibodies: perils and promise of development

Abstract

So far, most monoclonal antibodies have been developed for treating cancer or immunological diseases. However, the global spread of infections such as West Nile and corona viruses, and the need to address the potential threat of bioterrorism, has boosted public interest in, and government support of, counter-measures for infectious diseases. The attractive features of monoclonal antibodies, such as high specificity and effective recruitment of the immune system, would seem to make them excellent candidates as anti-infective agents. Here, we analyse trends in the development and approval of anti-infective monoclonal antibodies, and discuss factors that influence their success.

Phase I Evaluation of the Safety and Pharmacokinetics of a Single-Dose Intravenous Injection of a Murine Monoclonal Antibody against Hantaan Virus in Healthy Volunteers

“…Serial blood samples were collected prior to dosing (0 h) and then at 0.5, 1,6,12,24,72,120,192,264, and 408 h postdosing. Serum samples were separated and stored frozen at Ϫ80°C until they were used for analysis.…”

“…Although more than a quarter century has elapsed since its discovery and despite persistent efforts to develop antiviral drugs and vaccines, safe and effective therapeutic agents for the treatment and/or prophylaxis of HFRS are not available (1,4). The recent development of monoclonal antibodies (MAbs) for the prophylaxis and therapy of respiratory syncytial virus infection has been remarkable (6). We believe that similar to the anti-respiratory syncytial virus antibody, a murine MAb directed against HTNV could be developed for clinical use for the treatment of HTNV infections.…”

Anticorps thérapeutiques et maladies infectieuses

“…Bien que les Acm dirigés contre des agents infectieux soient directement en compétition avec, d'une part les vaccins, et d'autre part les petites molécules antivirales ou les antibiotiques [7], il existe une place pour ce type d'approche, en particulier lorsqu'aucun vaccin n'existe, comme par exemple pour l'infection par le VRS (Synagis®, sur le marché) ou le VIH (PRO 140, Mab anti-CCR5 en essai clinique de phase II). Il y a actuellement une vingtaine d'essais cliniques testant des Acm dans le domaine infectieux.…”

Preclinical development of monoclonal antibodies

“…Currently, there is only one approved mAb for a viral antigen, although there are a number in development, for example for hepatitis C virus and human immunodeficiency virus. 29,30 Palivizumab targets respiratory syncytial virus (RSV), and is used as treatment for lower respiratory tract illness in patients at high risk of experiencing severe symptoms, such as premature infants. The preclinical package for palivizumab was limited to PK (NHP), single dose toxicity (rat and NHP) and tolerance studies (rabbit).…”