biostudies-literatureKlechevsky ENIAID NIH HHSNCI NIH HHS6360-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC2728007biostudies-literatureUnknown68(15)In this study, we have explored the use of Fab-toxin proteins (immunotoxin) to target antigen-specific MHC-peptide complexes of in vitro and in vivo cancer cells. A human phage display library was used to screen for T-cell receptor (TCR)-like antibodies that are highly specific for the peptide melanoma-associated antigen MART-1(26-35) presented by HLA-A201. We also used previously selected TCR-like antibodies specific for the peptide melanoma-associated antigen gp100(280-288) presented by HLA-A201. The recombinant immunotoxin constructs were generated by fusing the targeting Fab fragment to a truncated form of Pseudomonas exotoxin, PE38KDEL. These immunotoxins bound with high affinity to the EBV-transformed JY cell line pulsed with the aforementioned peptides and internalized within 30 minCancer researchAntitumor activity of immunotoxins with T-cell receptor-like specificity against human melanoma xenografts.PMC2728007R0-1 CA78846P01 CA084512-069004P01 CA084512-069002P01 CA084512-01A10003P0-1 CA84512U19 AI057234-03U19 AI057234-04U19 AI057234-05R0-1 CA85540U19 AI057234-01U19 AI057234-02U19 AI057234-010005U19 AI057234-010004P01 CA084512-020003R01 CA085540-02R01 CA085540-03R01 CA085540-04R0-1 CA115550U19 AI057234-05S19003R01 CA115550-03R01 CA115550-04R01 CA115550-01R01 CA115550-02U19 AI057234-05S1U19 AI057234-05S10012U19 AI057234R01 CA078846U-19 AI-57234R01 CA078846-10P01 CA084512P01 CA084512-040003P01 CA084512-060005P01 CA084512-05A29004P01 CA084512-05A29002R01 CA078846-01A1P01 CA084512-05A2R01 CA115550P01 CA084512-07P01 CA084512-030003P01 CA084512-06R01 CA078846-09R01 CA078846-08R01 CA078846-07P01 CA084512-070005R01 CA078846-06R01 CA078846-05P01 CA084512-05A20005R01 CA078846-04R01 CA078846-03R01 CA078846-02R01 CA085540P01 CA084512-079002R01 CA085540-01A1P01 CA084512-079004Denkberg GReiter YKlechevsky EGallegos MPalucka KCohen CBanchereau JfalseAntitumor activity of immunotoxins with T-cell receptor-like specificity against human melanoma xenografts.In this study, we have explored the use of Fab-toxin proteins (immunotoxin) to target antigen-specific MHC-peptide complexes of in vitro and in vivo cancer cells. A human phage display library was used to screen for T-cell receptor (TCR)-like antibodies that are highly specific for the peptide melanoma-associated antigen MART-1(26-35) presented by HLA-A201. We also used previously selected TCR-like antibodies specific for the peptide melanoma-associated antigen gp100(280-288) presented by HLA-A201. The recombinant immunotoxin constructs were generated by fusing the targeting Fab fragment to a truncated form of Pseudomonas exotoxin, PE38KDEL. These immunotoxins bound with high affinity to the EBV-transformed JY cell line pulsed with the aforementioned peptides and internalized within 30 min2008-01-01T00:00:00Z2008 Aug2025-04-04T09:10:34.851Z2019-03-27T00:24:18ZS-EPMC27280071867686110.1158/0008-5472.can-08-092810.1158/0008-5472.CAN-08-0928