Recombinant single‐chain and disulfide‐stabilized Fv‐immunotoxins that cause complete regression of a human colon cancer xenograft in nude mice

Abstract

, 1988). New types of recombiriant Fv-immunotoxins were constructed in which the V H -V~ heterodimer is stabilized by an interchain disulfide bond engineered into structurally conserved framework residues of VH and VL (Brinkmann et al., 1993; Reiter et al., 19946,~). These types of molecules were termed disulfide stabilized Fvs(dsFvs) and dsFv-immunotoxins. They have good and in some cases improved activity in witro and in vivo cornpared with the corresponding scFv-immunotoxins (Reiter et al., 1994a,d;Benhar and Pastan, 1995). The targeting moiety (in scFv or dsFv form) is usually fused to a truncated form of Pseudornonas exotoxin but can also be fused to diphtheria toxin.

Production of anti‐cancer immunotoxins in algae: Ribosome inactivating proteins as fusion partners

“…Bacterial expression systems currently used to produce these fusion proteins are hampered by their inability to produce molecules that are more complex than scFv‐toxin fusions. Additionally, scFv‐toxin fusions produced in bacteria accumulate as insoluble aggregates, complicating the purification process by requiring that these proteins be denatured and re‐folded ex vivo (Reiter et al, ). These limitations make the bacterial expression route less than ideal.…”

Immunotoxins and Recombinant Immunotoxins in Cancer Therapy

“…Other recombinant immunotoxins that have been constructed and have antitumor activities in vitro and in mouse models in vivo include: B1(Fv)±PE38, also directed against the LeY antigen [112]; 55.1(Fv)±PE38 and 55.1(dsFv)±PE38, which are directed at a carbohydrate mucin antigen over-expressed in colon cancers [84]; MR1(Fv)±PE38, constructed by antibody phage-display technology and directed to a mutant EGF receptor over-expressed in liver and brain tumors [113]; and SS(Fv)±PE38, a new recombinant immunotoxin specific for mesothelin, a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers [114]. SS(Fv)±PE38 was constructed from an Fv fragment that was isolated by antibody phage display from mice that underwent DNA immunization with a plasmid expressing the cloned antigen [114].…”

Recombinant toxins in haematologic malignancies and solid tumours

“…mAb 55.1, recognising a different colon cancer antigen, could be converted to either an scFv or a dsFv fused to PE38 or PE38KDEL, and CRs were observed upon iv. treatment of tumour-bearing mice [248].…”