Methods for treating cancer with hyperactive adar enzymes

Abstract

The inventors hypothesized that the induction of a multitude of neoantigens in tumor cells, through hundreds of thousands of RNA editing events, would render tumors more recognizable by the patient's own T cells and that this could serve as an off-the-shelf therapeutic and could enhance the efficacy of immunotherapies. Example 1 provides evidence of therapeutic efficacy by locally delivering a hyperactive adenosine-to-inosine (A-to-I) RNA editing enzyme (ADAR) to induce neoantigens and to increase the effectiveness of immunotherapies. Accordingly, aspects of the disclosure relate to a method for treating cancer in a subject comprising administering a composition comprising a polypeptide comprising an adenosine deaminase RNA-specific binding protein (ADAR) or a nucleic acid encoding a polypeptide comprising an adenosine deaminase RNA-specific binding protein (ADAR), wherein the composition is administered in combination with an immunotherapy; and wherein the ADAR comprises a hyperactive ADAR.

Dependencies are inferred from the claim text.