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Review
. 2019 Sep 25:52:42-53.
doi: 10.1016/j.nbt.2019.04.002. Epub 2019 Apr 13.

Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation

Patrizia Murer  1 , Dario Neri  2
Affiliations
Review

Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation

Patrizia Murer et al. N Biotechnol. .

Abstract

Antibody-cytokine fusion proteins represent a novel class of biopharmaceuticals, with the potential to increase the therapeutic index of cytokine 'payloads' and to promote leukocyte infiltration at the site of disease. In this review, we present a survey of immunocytokines that have been used in preclinical models of cancer and in clinical trials. In particular, we highlight how antibody format, choice of target antigen and cytokine engineering, as well as combination strategies, may have a profound impact on therapeutic performance. Moreover, by using anti-inflammatory cytokines, antibody fusion strategies can conveniently be employed for the treatment of auto-immune and chronic inflammatory conditions.

Keywords: Antibody-fusion proeins; Cancer; Chronic inflammation; Cytokines; Immunemodulation; Immunocytokines; Immunotherapy; Targeted delivery.

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Figures

Figure 1
Figure 1
Schematic illustration of different antibody formats suitable for antibody-cytokine fusion proteins. From the left: full immunoglobulin (IgG), Small immunoprotein (SIP), scFv-FC, scFv, Diabody. N = N-terminus, C = C-terminus.
Figure 2
Figure 2
Examples of immunocytokines built with multiple subunits. a) Homotrimeric scFv-TNF [26, 71]. b) Left: scFv fused to single chain TNF (scTNF). Right: Homodimeric immunocytokine formed by two diabody-scTRAIL subunits. Other TNF superfamily cytokines can be engineered with the same approach [28, 154]. c) The C-terminus of the p40 is connected to the N-Terminus of the p35 subunits of IL12 15 amino acid linker. The recombinant cytokine is linked to the N-terminus of a scFv [7]. d) IL12-based immunocytokine consisting of two polypeptides, scFv-p35 and p40-scFv, joined by a disulfide bond between the two cytokine subunits[32]. e) IL12-SIP with a C-terminal CH4 domain of human IgE, wich favor homodimerisation. f) The p40 and p35 subunits of IL12 sequentially fused to a “forced” diabody or tandem diabody [17].
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