Expression in algae of a chimeric protein carrying several epitopes from tumor associated antigens

Abstract

Immunotherapies for cancer treatment constitute promising avenues to fight this global health issue. Algae can be used as both biofactories and delivery vehicles of vaccines; having low cost, fast growth, enhanced safety, and adjuvant effects as advantages. In the present study a multiepitope protein, called BCB, was designed as an attractive approach to develop new cancer immunotherapies. The BCB protein targets epitopes from the following tumor-associated antigens: human epidermal growth factor receptor-2 (HER2), mucin-like glycoprotein 1 (MUC1), Wilms' tumor antigen (WT1), and mammaglobin. Moreover, the BCB protein is based on the B subunit of the heat labile E. coli enterotoxin as immunogenic carrier to brake tolerance against self-antigens. A synthetic BCB-coding gene was obtained and expressed in Schizochytrium sp. using the Algevir system. The BCB protein was successfully expressed in transformed algae at levels up to 637 μg/g fresh weight, retaining the GM1-binding activity. The algae-made BCB showed reactivity towards an anti-serum against the tumor cell line 4T1; evidencing its antigenicity. Moreover the immunogenicity was evidenced in mice immunized with BCB, which developed serum IgG antibodies reacting against the 4T1 lysate. This study constitutes the first step in the development of innovative algae-based vaccines against cancer.