DNA vaccines for B-cell lymphomas: Towards personalised medicine and tailored drugs

DNA vaccine platform has produced exciting results in a wide array of applications, from prophylactic vaccine strategies to potential therapeutics targeting cancers and infectious disease (Fioretti et al., 2010, Rinaldi et al., 2009, Rinaldi et al., 2006 and Fazio et al., 2004). Many tumor antigens are excellent targets for active immunotherapy and can be presented by DNA vaccines in a molecular form suitable to engage both humoral and cellular immune responses. Our group is involved in the development of DNA vaccination strategies as active immunotherapy for the treatment of B-cell lymphomas. The idiotype region in the immunoglobulin expressed on the surface of B-cell lymphomas is a tumour-specific as well a patient-specific antigen and an ideal target for personalised immunotherapy. We focused on the idiotypic determinants lying within the CDR3 hypervariable regions and demonstrated that immunisation with CDR3-based DNA vaccines elicited anti-idiotypic humoral response able to recognize native antigens on tumour cells (Rinaldi et al., 2001). In a highly aggressive preclinical murine B-cell lymphoma model, we evaluated the antitumour response recruited by CDR3-based DNA vaccines. We showed that a combination of CDR3-based DNA vaccines with electroporation in a homologous prime-boost approach was protective against a lethal tumour challenge (Rinaldi et al., 2008 and Iurescia et al., 2010). Since a goal of our studies is the development of tailored immunisation strategies against previously established tumours, efforts are ongoing to optimize the DNA vaccine technology platform. Strategies to improve antigen expression and immunogenicity involve epitope prediction, MHC I presentation enhancement, inclusion of pathogen-derived sequences aimed to stimulate CD4+ T cell help and immunomodulating cytokines. Preliminary results encourage the use of therapeutic protocols based on DNA vaccines as tailored drugs for the treatment of lymphoma. Optimal integration of active immunization approaches into standard therapies suggests DNA vaccination as an effective personalized medicine to eradicate minimal residual diseases during clinical remission following standard chemotherapy in lymphoma patients.