A comparison of systemic versus targeted anti-TNFα antibody in treatment of colitis induced by adoptive transfer of CD44-/CD62L+ T-cells into RAG2-/- mice recipients

The development of therapies targeting the proinflammatory cytokine TNFα, such as infliximab, adalimumab, and others, has revolutionized the treatment of inflammatory bowel disease, which is characterized by a disproportionate inflammatory response in gastrointestinal tissues leading to damage and clinical symptoms.

These antibodies bind soluble TNFα, thereby blocking receptor binding and subsequent cytokine-driven inflammatory processes. In addition, when anti-TNFα antibodies bind transmembrane TNFα, many are capable of targeted cell death through antibody-dependent cell-mediated cytotoxicity.

Human studies have shown there is inadequate anti-TNFα antibody reaching the diseased tissue and the high TNFα burden is not adequately suppressed, resulting in persistent inflammation.¹ Thus, we hypothesized that anatomically targeted, topical administration of anti-TNFα antibody to the gastrointestinal tract would result in improved efficacy. In this study, we evaluated the efficacy of targeted, intracecal delivery of anti-mouse-TNFα antibody (a surrogate for human anti-TNFα antibodies) compared with systemic intraperitoneal injection in a chronic colitis mouse model.