Cytotoxins directed to interleukin-4 receptors have shown to mediate relatively selective @entity137 against a variety of @entity1 @entity5 cells in vitro and in vivo. In an ongoing Phase I clinical trial, a recombinant protein comprised of circularly permuted @entity3646 fused to a mutated form of Pseudomonas exotoxin (the fusion protein termed @entity3646 (38-37)-PE38KDEL or cpIL4-PE) has shown antitumour activity against @entity11 . @entity1 @entity2946 are @entity5 that occur in @entity1 and have a poor prognosis. The goal of this study was to determine whether @entity1 @entity2946 derived cell lines express @entity9597 and whether @entity9597 expression is accompanied by sensitivity to cpIL4-PE. @entity2946 cell lines express @entity9597 at the protein and mRNA levels as determined by binding, indirect immunofluorescence and RT--PCR studies. These cells expressed @entity9597 (also known as IL-4Rbeta) and IL-13Ralpha1 (also known as IL-13Ralpha') chains, however common gamma(c), a component of the @entity9597 system in immune cells was not detected. Consistent with the expression of @entity9597 , cpIL4-PE was found to be highly and specifically cytotoxic to four of five @entity2946 cell lines. Susceptibility of @entity2946 cell lines to cpIL4-PE seemed to correlate closely to the functional @entity3646 binding sites in general as demonstrated by 125I- @entity3646 binding, but did not seem to correlate with mRNA or cell surface immunoreactive receptor protein expression. The sensitivity of @entity2946 cells to cpIL4-PE could be eliminated by concurrent incubation with @entity3646 or @entity4047 , but not with @entity1199 . None of these cell lines showed any change in proliferation upon treatment with exogenous @entity3646 . These studies establish the @entity9597 as a @entity2946 -associated target for possible @entity5 -directed @entity5 therapy. Further studies are warranted to investigate @entity9597 expression in primary @entity5 and sensitivity to cpIL-4PE in vitro and in vivo.

@entity3646 receptors on XXXX @entity5 serve as a sensitive target for a circular permuted @entity3646 -Pseudomonas exotoxin fusion protein.

@entity1 :: ('9606', 'Species') :: ['children', 'human', 'Human'] @entity137 :: ('MESH:D064420', 'Disease') :: ['cytotoxicity'] @entity9597 :: ('3566', 'Gene') :: ['IL-4Ralpha', 'IL-4R', 'interleukin-4 receptor'] @entity4047 :: ('3596', 'Gene') :: ['IL-13'] @entity5 :: ('MESH:D009369', 'Disease') :: ['neuroectodermal tumours', 'medulloblastoma tumours', 'cancer', 'tumour'] @entity11 :: ('MESH:D005910', 'Disease') :: ['malignant glioma'] @entity1199 :: ('3558', 'Gene') :: ['IL-2'] @entity3646 :: ('3565', 'Gene') :: ['IL-4'] @entity2946 :: ('MESH:D008527', 'Disease') :: ['medulloblastoma', 'Medulloblastoma', 'medulloblastomas']
@entity1 :: (9606,Species) :: ['human']
