Recombinant Immunotoxin Therapy of Glioblastoma: Smart Design, Key Findings, and Specific Challenges

Table 1

Preclinical development of recombinant immunotoxins (RITs) for glioblastoma therapy.

Constructs of RITs	Targeting moiety	Toxin moiety	Target	Ref.
EGFR/EGFRvIII-targeted RITs
D2C7-(scdsFv)-PE38KDEL (D2C7-IT)	D2C7 scFv	PE38KDEL	EGFR/EGFRvIII	[60–63]
MR1(Fv)-PE38 (MR1)	MR1 scFv	PE38	EGFR/EGFRvIII	[64–67]
MR1-1(Fv)-PE38 (MR1-1)	Mutated MR1 scFv	PE38	EGFR/EGFRvIII	[57, 66]
TGFα-PE38 (TP38)	Transforming growth factor α	PE38	EGFR	[68–71]
TGFα-PE40 (TP40)	Transforming growth factor α	PE40	EGFR	[72–74]
DAB389EGF	EGF	DAB389	EGFR	[75–80]
DT390-BiscFv806	mAb806 biscFv	DT390	EGFR/EGFRvIII	[81]
ScFv(14E1)-ETA	mAb14E scFv	PE40	EGFR/EGFRvIII	[82–85]
Anti-EGFR/LP1	Anti-EGFR scFv	Plant Luffin P1	EFGR	[86]
IL-13R and IL-4-targeted RITs
IL-13PE38QQR (IL-13PE)	IL-13	PE38QQR	IL-13R	[87–89]
IL13E13K-PE38	Mutated IL-13	PE38QQR	IL-13R	[88, 90, 91]
Anti-IL-13Ra2(scFv)-PE38	Anti-IL-13Ra2 scFv	PE38	IL-13Ra2	[91, 92]
DT390IL13	IL-13	DT390	IL-13R	[93, 94]
IL4(38-37)-PE38KDEL (cpIL4-PE)	IL-4	PE38KDEL	IL-4R	[95, 96]
DT390-mIL4	11B11 scFv	DT390	IL-4R	[97]
Bispecific RITs
DT390-ATF (DTAT)	uPA ATF	DT390	uPAR	[98–100]
DT390-IL-13-ATF (DTAT13)	uPA ATF and IL-13	DT390	uPAR/IL-13R	[100, 101]
EGFATFKDEL	uPA ATF and EGF	PE38KDEL	uPAR/EGFR	[102–104]
EGFATFKDEL7mut	uPA ATF and EGF	Mutated PE38KDEL	uPAR/EGFR	[102–104]
DTEGF13	IL-13 and EGF	DT390	IL-13R/EGFR	[105, 106]
Others
8H9scFv-PE38	mAb 8H9 scFv	PE38	B7H3	[107, 108]
EphrinA1-PE38QQR	EphrinA1	PE38QQR	EphA2 receptor	[109]
NZ-1-(scdsFv)-PE38KDEL	NZ-1 scFv	PE38KDEL	Podoplanin	[110]
DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT)	Mutated DmAb14 scFv	PE38KDEL	3′-isoLM1/3′,6′-isoLD1	[111]
IT-87	VLCDR1–VHFR2–VHCDR3	DT388	BT32/A6	[112]