Split-immunotoxins for boosting oncolytic virus toxicity

Abstract

As disclosed herein, the assistance of a new generation of immunotoxins (split-immunotoxins) the range of cancers susceptible to elimination by oncolytic viruses and the specific toxicity of the latter can be expanded without compromising the selectivity of targeting. To accomplish this goal, a polypeptide chain of a potent bacterial toxin (including, but not limited to a catalytic subunit of a Diphtheria toxin, DTA) can be split into two benign parts, which can then be delivered to the cytoplasm of cancer cells via two independent cancer-specific pathways: (1) together with an oncolytic virus (encoded in its genome); (2) as a split-immunotoxin delivered via receptor-specific toxin entry pathways. The two parts are fused into a functional toxin only in the cytoplasm of dually targeted cancer cells by means of intein-catalyzed trans-splicing.

Dependencies are inferred from the claim text.