An Update in the Use of Antibodies to Treat Glioblastoma Multiforme

Table 1

Classification of clinically used toxins based on their mechanism of action.

Classification of toxins
Toxins	Source	Mechanism	Structure	Modifications	References
ADP ribosylating toxins
Diphtheria toxin	Corynebacterium diphtheria	ADP ribosylation of EF2	Activity (A chain),; translocation (T), and binding (B) domains	(a) DT486; (b) DT388 or DT389 (deletion of cell-binding domain); (c) CRM107 point (mutation in cell-binding domain of DT)	[10–13]
Pseudomonas exotoxin	Pseudomonas aeroginosa	ADP ribosylation of EF2	Binding (Ia), translocation (II and Ib), and activity domains (III)	(a) PE40 and PE40KDEL; (b) PE38 and PE38KDEL; (c) PE38QQR; (d) PE35	[10, 13–15]
Pore-forming toxins
Cholera toxin	Vibrio cholera	ADP ribosylation of Gs, a subunit of G protein	Activity (A chain) and cell-binding domains (pentameric B chain)	CET40 (domains II and III)	[13, 16, 17]
Ribosome inactivating toxins
Holotoxins-ricin	Ricinus communis	N-glycosylation of 28S rRNA	Activity and binding domains	(a) Ricin; (b) Ricin A chain (RTA); (c) bR (blocked ricin); (d) dgA (deglycosylated; ricin A chain)	[13, 18]
Hemitoxins-saporin (SAP),; pokeweed antiviral; protein (PAP)	Saponaria officinalis, Phytolacca; americana	N-glycosylation; of 28S rRNA	Single-chain proteins; without binding domain		[13, 19]
Ribonucleases
Fungal toxins-a-sarcin, restrictocin; HPR, ECP, EDN	Aspergillus sp.; Human	Cleavage of 28S rRNA; Degradation of RNA	Single-chain proteins without binding domain; Single-chain proteins		[13, 19]; [13, 20]

Some immunotoxins are presented which have been used as toxin-based therapeutic approaches in the treatment of several malignancies acting on different intracellular targets. ADP: adenosine diphosphate; EF2: elongation factor 2 during protein synthesis on the ribosome; DT: diphtheria toxin; DT388 or DT389: truncated forms of DT without the receptor-binding activity; CRM107: cross-reacting material-mutant of DT without the receptor binding; PE: Pseudomonas exotoxin A; PE40 and PE38: truncated forms of PE without the receptor-binding domain Ia; CET40: cholera exotoxin A; RTA: ricin toxin A; HPR: human pancreatic ribonuclease A; ECP: eosinophilic cationic protein; EDN: eosinophil-derived neurotoxin.