Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model
AbstractVaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against cancer and has already shown promise in the clinical setting. Conventional plasmid DNA is commonly used which together with the encoded antigen also includes bacterial immunostimulatory CpG motifs to target the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNA ™), have been developed without the use of bacteria. The cell-free process relies on the use of Phi29 DNA polymerase to amplify the template followed by protelomerase TelN to complete individual closed linear DNA. The resulting DNA contains the required antigenic sequence, a promoter and a poly A tail but lacks bacterial sequences such as an antibiotic resistance gene, prompting the question of immunogenicity. Here we compared the ability of doggybone DNA vaccine with plasmid DNA vaccine to induce adaptive immunity using clinically relevant oncotargets E6 and E7 from HPV. We demonstrate that despite the inability to trigger TLR9, doggybone DNA was able to induce similar levels of cellular and humoral immunity as plasmid DNA, with suppression of established TC-1 tumours.
In the last years, immunotherapies have shown tremendous success as treatments for multiple types of cancer. However, there are still many obstacles to overcome in order to increase response rates and identify effective therapies for every individual patient. Since there are many possibilities to boost a patient’s immune response against a tumor and not all can be covered, this review is focused on T cell receptor-mediated therapies. CD8+ T cells can detect and destroy malignant cells by binding to peptides presented on cell surfaces by MHC (major histocompatibility complex) class I molecules. CD4+ T cells can also m...
This study aimed to improve WCTVs with xenoantigens to end immune tolerance and to further activate the adaptive immune system. In the present study, we designed a WCTV by transducing a vector encoding human FAPα (hFAPα) into murine tumour cells and evaluated its efficacy in multiple solid tumour models. Immunotherapy with this WCTV effectively delayed tumour growth and prevented recurrence. The anti-tumour responses were clearly linked to antigen-specific cytotoxic T cells, whereas CD4(+) T lymphocytes also played a role. Humoural immune responses were activated because the adoptive transfer of immunoglobulins...
ConclusionThus, in one volunteer we show a granuloma forming by peptides combined with an efficient adjuvant in a water-in-oil-emulsion, inducing antigen specific T cells detectable in circulation and at the vaccination site, after one single vaccination only. The ex vivo T cell responses in peripheral blood were detectable for more than one year and could be strongly boosted by a second vaccination. Hence, XS15 is a promising adjuvant candidate for peptide vaccination, in particular for tumor peptide vaccines in a personalized setting.
ConclusionsImmunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.Trial registrationClinicalTrials.gov identifierNCT02692976, registered 26 February 2016, retrospectively registered.
Cancer immunotherapy including adoptive T cell therapy (ACT) is widely used in the clinic and is highly beneficial for patients with hematological malignancies; however, it remains a challenge to develop effective immunotherapy strategies for the treatment of solid cancers, due to the inefficiency of the immune response and the immunosuppressive tumor microenvironment (TME). Immunogenic cell death (ICD) converts dying cancer cells into a therapeutic vaccine and stimulate a systemic antigen-specific antitumor immune response, which can effectively subvert the immunosuppressive TME and enhance the efficiency of immune respon...
Conditions: Merkel Cell Carcinoma; Cutaneous Squamous Cell Carcinoma Intervention: Biological: IFx-Hu2.0 Sponsors: Morphogenesis, Inc.; H. Lee Moffitt Cancer Center and Research Institute Recruiting
Conditions: Pancreatic Adenocarcinoma; Pancreatic Cancer Intervention: Biological: Autologous DC vaccine Sponsors: Baylor College of Medicine; Cancer Cures for Kids Not yet recruiting