Immunotherapy

Abstract

Immunotherapy implies the use of an immune-based therapy to treat infection. Broadly speaking, these therapies can be divided into antibody-based therapies (both pathogen specific and pathogen agnostic), cellular therapies (e.g. CMV-specific T cells), and immune signalling therapies (e.g. interferon-alpha in the treatment of hepatitis C infection). While agents such as corticosteroids, thalidomide, and vitamin D have profound effects on immune function and a well-established role in the treatment of some infections (e.g. corticosteroids in tuberculous and pneumococcal meningitis), in this review they are not considered as immunotherapy, as they are not directly derived from components of the immune system. When considering immunotherapy, it is important to make a distinction between therapy and prophylaxis. There are well-established indications for using immunotherapy as prophylaxis against infection, including the use of varicella immune globulin and RSV-specific monoclonal antibodies (Palivizumab) to prevent chicken pox and RSV infection respectively. In addition, immunization is a form of immunotherapy—inducing a primary immune response and immunological memory such that on exposure to the pathogen, a secondary immune response is rapidly generated, hopefully leading to the control and eradication of the pathogen before infection occurs. There are few immunotherapies currently in routine clinical use, and several experimental therapies under investigation. The aim of most immunotherapy is to replicate what should happen in an effective immune response to a pathogen, but which, due to host factors, pathogen factors, or both, has failed to occur. Antibodies exert their effect in three main ways: 1. Neutralization: Antibody binding to pathogens, or their toxins, limits the access of the pathogen or the toxin to the target cell, thereby preventing cell infection or damage. Neutralization is important for preventing viral entry into cells and preventing the actions of bacterial toxins, e.g. Staphylococcal exotoxin. Neutralization cannot prevent bacterial replication. 2. Antibody dependent cytotoxicity: Phagocytes express receptors for the Fc-portion of antibodies on their cell surface (FcRs). Ligation of phagocyte FcR with an antibody bound to a pathogen is an effective method of delivering a pathogen to a phagocyte for engulfment and destruction. Coating of pathogens with antibodies is a form of opsonization, or ‘making ready to eat’.