12 Recombinant lymphocytic choriomeningitis virus (rLCMV) was generated by reverse genetic engineering, i.e., the glycoprotein (GP) encoding sequence was replaced with a target antigen rendering the prototypic arenavirus propagation deficient. Absence of E1 in recombinant Ad (rAd) vectors limits replication within target cells. Replication-deficient Ad5 vectors are generated by substituting the early transcribed E1 and/or E3 regions with a transgene or vaccine antigen. 9, 10, 11 To ensure safety, viral replication and dissemination can be restricted by genetic manipulation of viral vectors.
6, 7, 8 Similarly, lymphocytic choriomeningitis virus (LCMV) has been shown to induce strong T cell responses by targeting dendritic cells without eliciting vector-specific antibodies and has recently been tested in a phase 1 clinical trial. Vaccination vectors based on recombinant human adenovirus serotype 5 (rAd5) have extensively been studied in the context of T cell vaccines directed against viral antigens.
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4, 5 These approaches aim at activating adaptive immune responses through priming of naive T cells against the vector encoded antigen by professional antigen presenting cells (APCs). 3 Current experimental vaccination protocols include peptides, cell-based vaccination, oncolytic viruses, or recombinant vectors. Infiltration of cytotoxic CD8 + T cells into the tumor has been shown to play a key role in control and eradication of tumors. To date there is no successful therapeutic cancer vaccine targeting shared self-antigens in patients with already existing tumors. 1, 2 However, those vaccinations are preventive vaccines that target viral antigens of oncogenic viruses. Cancer vaccines have successfully been applied for the prevention of cervical cancer and hepatocellular carcinoma by targeting human papillomavirus and hepatitis B virus, respectively. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model.Įfficient vaccination against cancer and infectious diseases relies on the induction of adaptive immune responses. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth.
A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8 + T cells. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100.
# 218327#GPUG Presenter Chris Dobkins – Njevity, the GP Experts and Creators of PowerGP Online # 173088#GPUG Presenter Jennifer Ranz – Microsoft # 165358#GPUG Presenter Errol Schoenfish – Microsoft # 221192#GPUG Presenter Rod O'Connor, MVP – Briware Solutions Inc.Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. # 254845#GPUG Presenter Charles Allen – BKD Technologies # 263237#GPUG Presenter Rob Klaproth, Dynamics Certified, Coupa Certified – Armanino LLP # 390515#GPUG Presenter Mariano M. # 181682#GPUG Presenter Tanya Henderson – S2Technology # 265210#GPUG Presenter Abra Lynne Gilman – Collins Computing, Inc. Bob McAdam – Dynamic Communities # 171141#General Session Speaker Jeff LaBelle – Donor Network of Arizona # 571709#GPUG Presenter Rick Zich – Coopers DIY # 254820#GPUG Presenter Lisa Lucas – Dynamic Communities # 436248#GPUG Presenter Windi Epperson, CPA, Multiple Dynamics Certifications – Advanced Integrators, Inc.