Supplementary Tables S1-S2 and Supplementary Figure S1 from Recombinant Immunotoxin with T-cell Epitope Mutations That Greatly Reduce Immunogenicity for Treatment of Mesothelin-Expressing Tumors

Mazor, Ronit; Zhang, Jingli; Xiang, Laiman; Addissie, Selamawit; Awuah, Prince; Beers, Richard; Hassan, Raffit; Pastan, Ira

doi:10.1158/1535-7163.22503261.v1

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Supplementary Tables S1-S2 and Supplementary Figure S1 from Recombinant Immunotoxin with T-cell Epitope Mutations That Greatly Reduce Immunogenicity for Treatment of Mesothelin-Expressing Tumors

journal contribution

posted on 2023-04-03, 14:42 authored by Ronit Mazor, Jingli Zhang, Laiman Xiang, Selamawit Addissie, Prince Awuah, Richard Beers, Raffit Hassan, Ira Pastan

Table S1. Cytotoxic activity in vitro in five cell lines; Table S2. In vivo toxicity of RITs; Fig S1. Cytotoxic activity in patients cells curves

History

ARTICLE ABSTRACT

SS1P is a recombinant immunotoxin (RIT) that targets mesothelin. It consists of an antimesothelin Fv fused to a portion of Pseudomonas exotoxin A. In clinical studies, it has produced dramatic responses in patients with advanced mesothelioma, when combined with immunosuppressive therapy so that several treatment cycles could be given. Otherwise its activity is limited by its immunogenicity. In this work, we describe the development and characterization of LMB-T20, a highly potent RIT targeted at mesothelin-expressing cancers with low immunogenicity due to removal of its eight T-cell epitopes. LMB-T20 was more active than SS1P when tested on four different mesothelin-expressing cell lines as well as on cells obtained from patients with mesothelioma. It also has potent antitumor activity in mice, and has reduced immunogenicity as measured by cytokine secretion assays. In conclusion, LMB-T20 is a favorable candidate for evaluation in clinical trials due to its reduced immunogenicity and excellent activity. Mol Cancer Ther; 14(12); 2789–96. ©2015 AACR.