Broad antigenic coverage induced by vaccination with virus-based cDNA libraries cures established tumors

Abstract

We show here that a cDNA library of normal tissue, expressed from a highly immunogenic viral platform, cures established tumors of the same histological type from which the cDNA library was derived. With suboptimal vaccination, immune escape was possible, but only when tumor cells were forced to acquire a radically new phenotype, readily treated by second line therapy. This approach has several major advantages. Use of the cDNA library leads to presentation of a broad repertoire of (undefined) tumor associated antigens, which reduces emergence of treatment resistant variants and also permits implementation of rational, combined modality approaches in the clinic. Finally, the viral vectors can be delivered systemically, without the need for tumor targeting, and are amenable to clinical grade production. Therefore, virus-expressed cDNA libraries represent a novel paradigm for cancer treatment by addressing many of the key issues which have undermined the efficacy of immuno/virotherapy to date.