Immunocytokines: a novel class of products for the treatment of chronic inflammation and autoimmune conditions

Abstract

Antibody-cytokine fusion proteins, often referred to as immunocytokines, represent a novel class of biopharmaceutical agents that combine the disease-homing activity of certain antibodies with the immunomodulatory properties of cytokine payloads. Originally, immunocytokines were mainly developed for cancer therapy applications. More recently, however, the use of anti-inflammatory cytokines for the treatment of chronic inflammatory conditions and to treat autoimmune diseases has been considered. This review analyzes basic principles in the design of immunocytokines and describes the most advanced products in preclinical and clinical development.

Figure 1

(a) Schematic illustration of different recombinant binding moiety formats suitable for immunocytokine development. (b) Frequently used immunocytokine formats, including IgG heavy chain fusion, IgG light chain fusion, C- and N-terminal diabody fusion, C- and N-terminal scFv fusion (left to right). C: cytokine. (c) Various immunocytokine formats for heterodimeric cytokine payloads, which have been used for the development of IL12-based immunocytokines [8,42].

Figure 2

Pharmacodelivery applications for monoclonal antibodies, specific to the extra-domain A (EDA) of fibronectin, an antigen that is virtually undetectable in normal adult tissues [87]. Tissue stainings adapted, with permission, from [46,57,59,61,62,67].