Harnessing the power of foot-and-mouth-disease virus for targeting integrin alpha-v beta-6 for the therapy of cancer

Figures & data

Figure 1. 3D Structure of A20 peptides. A20FMDV2 and A20LAP STD NMR transfer maps onto the averaged helical structures of these peptides illustrate a defined high definition contact face on each peptide. The ability of these peptides to easily form helices is important for enhanced efficacy toward αvβ6 as helix formation proves a structural definition of a face of amino acids that includes the side chains of the extended LXXL motif as well as residues further toward the C-terminus of these sequences. In contrast the A20FMDV1 structure does not present a clear RGDLXXL interface, presumed to be because of the poor helix forming C-terminus. (Data generated and analyzed by Dr Mark Howard, University of Leeds)

Table 1. Chemical modifications of A20FMDV2 to improve its biodistribution

Name/Sequence	Modification	Effect	Reference
[18 F]FBA-A20FMDV2	n/a	First A20FMDV2 peptide used for PET imaging	[60]
[^18F]FBA-PEG28-A20FMDV2	PEG linker	PEG linker resulted in clearer imaging as nonspecific binding was significantly improved	[19]
[18F]FBA-C6-ADIBON3-PEG7- A20FMDV2	Copper-free click chemistry used to generate peptide	Although peptide more stable, poorer pharmacokinetics	[35]
18F-FBA-PEG28-A20FMDV2-PEG28	Size and location of PEG linker changed	Size and location of PEGs affects pharmacokinetics. Bi-PEGylated peptide leading candidate for further optimizations.	[20]
A20FMDV2	N-terminal d-Asn, C-terminal d-Thr	Improved serum stability and relative activity	[34]

Table 2. Oncolytic viruses incorporating A20FMDV2

Name	Summary	Reference
Ad5-A20	First A20FMDV2 virus, proof of concept for αvβ6 targeting oncolytic virus	[44]
Ad5-477dlTAYT(A20)	TAYT mutation incorporated to reduce CAR binding	[37]
Ad5/48kn-A20	A20FMDV2 incorporated into fiber knob of AD48, to create AD5/48 pseudotype	[47]
Ad5-KO1-A20	KO1 mutation incorporated to reduce CAR binding	[47]
Ad5-3Δ-A20T	A TAYT mutation and A20FMDV2 incorporated into fiber knob of AdΔΔ; an Ad designed to reduce CAR binding	[49]

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