Table 1.

TRAIL modifications that enable detection and/or improve therapeutic performance.

Name	Modification	Improvement	Application	Refs
LZ-TRAIL	Addition of a leucine zipper	Efficacy	Facilitated trimerization, activity and stability in vitro and in vivo	[8]
[125I]rhTRAIL	Radioiodinated recombinant human TRAIL	Detection	In vivo biodistribution and clearance	[18]
FLAG-TRAIL	Addition of FLAG tag to TRAIL	Efficacy	FLAG tag allows cross linking of TRAIL by using an anti-FLAG antibody	[19]
S-TRAIL-GFP	Fusion of the extracellular domain of Flt3L and an isoleucine zipper to the N-terminus of TRAIL. GFP fused to C-terminus	Efficacy + Detection	Enhanced apoptosis via bystander effect and stabilized oligomerization of TRAIL. GFP expression allows visualization of TRAIL-expressing cells	[20]
iz-TRAIL	Addition of an isoleucine zipper	Efficacy	Facilitated oligomerization resulting in improved cytotoxicity	[21]
scFv-sTRAIL	scFv-sTRAIL bifunctional fusion proteins	Efficacy	Increased specificity and strength of TRAIL response. Permits paracrine signaling	[23, 69]
HSA-Flag-TNC-TRAIL	Human serum albumin genetically fused to N-terminus of secretable TRAIL	Efficacy	Increased serum halflife to improve bioavailability	[24]
Transferrin-PEG-TRAIL (Tf-PEG10K-TRAIL)	PEGylated TRAIL attached to transferrin	Efficacy + Targeting	Combined tumor targeting/killing properties	[25]
PEG-TRAIL	PEGylation of TRAIL with PEGa of different molecular weights	Efficacy + Longevity	Increased serum half-life and protracted activity in vivo	[26]
TRAIL-loaded PLGAb microspheres	Nanocomplex system	Efficacy + Longevity	Sustained TRAIL release and tumor killing properties in vivo	[27]
SRL0L2TR	Luciferase fused to the N-terminus of secretable TRAIL	Detection	Direct extracellular visualization and monitoring of levels, time of delivery and localization of stem cell-delivered proteins by bioluminescent imaging	[38]
pORF-hTRAIL	Multifunctional nanoparticle comprising doxorubicin (DOX) and pORF-hTRAIL	Efficacy	Anti-glioma efficacy in vivo. Low pH conditions, such as those found in tumors, result in fast DOX release via cleavage of a pH-sensitive hydrazine bond	[49]
TRAIL-UCA	Ultrasound contrast agents chemically conjugated to TRAIL	Detection	Tracked by ultrasound imaging and fragmented into nanoparticles by focused ultrasound	[71]
Nanoparticle-TRAIL	TRAIL conjugated to nanoparticles	Efficacy	Enhances anti-tumor activity in glioma and glioma stem cells in vitro and in vivo	[72]

^aPEG, Polyethylene glycol.

^bPLGA, poly(lactic-co-glycolic acid).