Pseudomonas Exotoxin Immunotoxins and Anti-Tumor Immunity: From Observations at the Patient's Bedside to Evaluation in Preclinical Models.

ABSTRACT: Immunotoxins are protein drugs composed of a targeting domain genetically fused to a protein toxin. One killing domain being explored is a truncated Pseudomonas exotoxin A (PE). PE based immunotoxins are designed to kill cells directly by inhibiting their ability to synthesize proteins. However, observations from clinical trials suggest that this alone cannot explain their anti-tumor activity. Here we discuss patterns of clinical responses suggesting that PE immunotoxins can provoke anti-tumor immunity, and review murine models that further support this ability. In addition, we describe our preclinical effort to develop a combination therapy of local PE immunotoxins with a systemic anti-CTLA-4 immune check point blocking antibody. The combination eradicated murine tumors and prolonged the

SUBMITTER: Leshem Y 

PROVIDER: S-EPMC6356957 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature