Vandenbroucke K, de Haard H, Beirnaert E et al. Mucosal Immunol 2010;3:49–56.
In this study, a bacterium (Lactococcus lactis) was engineered to synthesize and secrete anti-tumor necrosis factor (anti-TNF) nanobodies (single-domain antibody fragments); this function was confirmed in vitro. These bacteria were then given to mice with dextran sodium sulfate (DSS)-induced colitis. This resulted in effective delivery of the anti-TNF nanobody to the affected colon. Moreover, L lactis treatment effectively ameliorated chronic colitis in both the DSS-induced and interleukin-10-knockout murine colitis models. This local delivery system may be less toxic than systemic therapy; treated animals were comparable to controls in terms of their handling of systemic Salmonella infection.
The efficacy of the anti-tumor necrosis factor (anti-TNF) agents is well established in Crohn’s disease and, to a lesser extent, ulcerative colitis (UC). The currently available antibodies (adalimumab, infliximab, and certolizumab) are all delivered systemically via intravenous or subcutaneous injection. As a result, there is a modest, but definite increase in (opportunistic) infectious complications in treated individuals. Targeted local delivery of anti-TNF therapy may therefore be advantageous. However, it is not possible to simply administer antibodies via oral or rectal routes.