Research Focus

Identification and clinical exploitation of mutated neoantigens expressed at high frequency in the patient’s disseminated tumor lesions is facing significant hurdles. Here we describe an approach whereby universal antigens are induced in tumor cells in situ by transient downregulation of the peptide transporter TAP. Administration of TAP siRNA conjugated to a broad-range tumor-targeting nucleolin aptamer inhibited tumor growth in several tumor models without measurable toxicity, was comparatively effective to vaccination against prototypic spontaneous neoantigens, and induced the presentation of a TAP-independent peptide in human tumor cells. Treatment with this chemically-synthesized aptamer-siRNA conjugate represents a simple and broadly-applicable approach to transiently increase the antigenicity of tumor lesions and is expected to enhance the effectiveness of any immune potentiating therapy.