YVONNE J PATERSON

..In the past year it has been shown to be particularly effective as a tumor antigen vector. Here we set its potency as a cancer vaccine in the context of the type of immunity induced by this facultative intracellular bacterium...

..Safety issues associated with live bacterial vaccine vectors and problems to be overcome in developing Listeria as a cancer immunotherapeutic for human use are also discussed...

..This review also discusses safety issues associated with live bacterial vaccine vectors and problems to be overcome in developing Listeria as a HIV vaccine for human use...

..In the field of tumor immunotherapy, we are also developing nonliving vaccine vectors for tumor antigens...

..Here we describe differences in the properties of these bacteria as vaccine vectors, a summary of the major therapies they have been applied to and their advancement towards the clinic...

..In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor (TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease...

..CONCLUSIONS: Our findings identify a role for IFN-gamma in immunity to TC1 tumors and show that loss of tumor responsiveness to IFN-gamma poses a challenge to antigen-based immunotherapy...

..Thus, the Listeria vaccine vector presented here potentially complies with Food and Drug Administration regulations and could be developed further for clinical use...

..We believe that the identification of several immune parameters that correlate with antitumor efficacy, and of some that have a negative correlation, may have wider application for other cancer immunotherapeutic approaches...

..In addition, we found that after each passage, harvested bacteria must be cloned and checked for expression of the bioengineered gene to counter selection in favor of antigen loss mutants...

..In conclusion, a Lm-based vaccine against HMW-MAA can trigger cell-mediated immune responses to this antigen that can target not only tumor cells but also pericytes in the tumor vasculature...

..Safety issues and the transition of Listeria into human clinical trials will also be discussed in this review...

..The data presented in this report demonstrate that mucosally administered Listeria can prompt such a response and that booster doses can maintain this response...

..The aim of this study was to efficiently design a novel vaccine for human Her-2/neu-positive (hHer-2/neu) breast cancer using the live, attenuated bacterial vector Listeria monocytogenes...

..In particular, the review focuses on pathways leading to effector T cell penetration of tumors or the inhibition of this process...

..These findings suggest a strategy for the augmentation of tumor antigen-based immunotherapeutic strategies that may be broadly applicable...

..Because of its unique ability to induce a cellular immune response, the intracellular bacteria Listeria monocytogenes has been studied as a potential HPV-positive tumor vaccine...

..Taken together, the changes in DC expression correlate well with the differences in antitumor efficacy between these two vaccines...

..monocytogenes can induce a cellular immune response in a nonhuman primate and is able to enhance the efficacy of a DNA vaccine as well as provide modest protection against SIV239 challenge...

..These results show that it is possible for a tumor vaccine system to generate tumor-infiltrating CD4CD25 regulatory T cells that critically affect tumor regression and the overall success of vaccine therapy...

..Notably, the strategies employing both chimeric and bicistronic vaccines were effective in reducing tumor burden suggesting that LLO can act as an adjuvant that does not require fusion with the tumor antigen to mediate its effect...

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..monocytogenes-based HER-2/neu vaccines in a murine model of breast cancer and also that the immunogenicity of self-Ags can be increased by fusion to LLO and delivery by L. monocytogenes revealing subdominant epitopes...

..Oral immunization with both constructs resulted in diminished viral titers in the cervix and uterus of mice after intravaginal challenge with vaccinia virus expressing HPV-16-L1...

..Thus, vaccinia virus expressing foreign antigen incorporated into EEV may be a better vaccine strategy than standard recombinant vaccinia virus...

..This study shows that Listeria-based vaccines are able to slow autochthonous tumor growth and break immunological tolerance...

..We show that an anti-angiogenesis vaccine can overcome tolerance to the host vasculature driving epitope spreading to an endogenous tumor protein and drive active tumor regression...

..This study demonstrates the ability of L. monocytogenes-based vaccines to impact upon tolerance to HER-2/neu in FVB/N HER-2/neu transgenic mice and further defines some of the aspects of tolerance in these mice...

..In this model, Listeria-based vaccines against E7 appear to be overcoming central tolerance by expanding low avidity CD8+ T cells specific for E7 that are not deleted during thymopoesis and can eliminate solid tumors...

..In addition, HER-2/neu DNA vaccination followed by CTL analysis further showed that both of these peptides can emerge as epitopes...

..We are also exploring the role of Listerial virulence factors in potentiating adaptive immune responses by activating innate immunity. Specifically, we are using these proteins as adjuvants for B cell lymphomas...

..Thus, anti-Id vaccines incorporating LLO may be a better therapeutic option for treatment of B-cell lymphoma...

..The long delay in the onset of tumors after immunotherapy targeting the kinase domain may be because this region of HER-2/neu cannot undergo extensive mutations without impairing its ability to signal cell growth...

..Thus, the DNA prime-oral Listeria boost strategy induced a mucosal SIV-Gag-specific CD8 T cell response characterized by expression of the alpha4beta7 integrin gut-homing receptor...

..Further, this study demonstrates that as virus replicates the T cell immune response to SIV antigens induced by the vaccine is modulated by antigen encountered by immune cells during viral replication...

..This therapy is currently undergoing phase III clinical trials...

..The partner institution will have more research-oriented courses due to the investment of postdocs in course development. ..

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..Post-doctoral trainees are selected competively based on a national search. Recruitment of qualified, under-represented minorities takes a precedence in this endeavor. ..

..We will also have tested 3 possible adjuvants to enhance its delivery. This will set the stage for a Phase II proposal focused on preparations for entering clinical trials. ..

..This work will demonstrate the utility of the L. monocytogenes-based vaccines, thus setting the stage for further development of a breast cancer therapeutic that can be used in humans. ..

..The findings of these studies may be generally applicable to other cancer approaches and to the measurement of immune components that are indicative of good tumor immunotherapy. ..

..These studies will start in year 2 of the proposal. The hypothesis of this aim is that the attenuated strains will as effective as wild-type Listeria in delivering SHIV antigens to the immune system. ..

..In this specific aim we hypothesize that Lm- LLO-E7 will break tolerance in this mouse model and we will explore the mechanisms by which it does so. ..

..In this specific aim we hypothesize that Lm- LLO-E7 will break tolerance in this mouse model and we will explore the mechanisms by which it does so. ..

..monocytogenes, prior to the exploitation of this unique therapeutic human cancer. ..

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