Publications by authors named "Timo Schippers"

Background: Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenavirus family known for inducing strong cytotoxic T-cell responses in both mice and humans. LCMV has been engineered for the development of cancer immunotherapies, currently undergoing evaluation in phase I/II clinical trials. Initial findings have demonstrated safety and an exceptional ability to activate and expand tumor-specific T lymphocytes.

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Background: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8 T cells. Although the strong antigen-specific immune response elicited by artLCMV vectors has been demonstrated in several preclinical models, PICV-based vectors are much less characterized.

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Engineered viral vectors represent a promising strategy to trigger antigen-specific antitumor T cell responses. Arenaviruses have been widely studied because of their ability to elicit potent and protective T cell responses. Here, we provide an overview of a novel intravenously administered, replication-competent, non-lytic arenavirus-based vector technology that delivers tumor antigens to induce antigen-specific anti-cancer T cell responses.

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Article Synopsis
  • Cowpox virus (CPXV) can infect humans through animal hosts, with a notable outbreak in 2009 linked to pet rats.
  • A specific rat isolate, RatPox09, showed higher virulence and mortality rates compared to a less harmful laboratory strain, prompting research into four unique genes in RatPox09 that may enhance its efficacy.
  • Experiments using genetically modified variants of the BR strain revealed that these RatPox09 genes significantly increased virulence, especially one encoding the D7L protein, highlighting how a small number of genes can greatly impact the severity of CPXV infections.
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Unlabelled: Marek's disease virus (MDV), an alphaherpesvirus, is the causative agent of a lethal disease in chickens characterized by generalized nerve inflammation and rapid lymphoma development. The extensive colinearity of the MDV genome with those of related herpesviruses has eased functional characterization of many MDV genes. However, MDV carries a number of unique open reading frames (ORFs) that have not yet been investigated regarding their coding potentials and the functions of their products.

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We have identified a highly transformable strain of Actinobacillus pleuropneumoniae whose competence is regulated by the competence-activator Sxy as in other Pasteurellaceae. Other strains were poorly transformable or nontransformable. The genomes of two poorly transformable strains contain intact sets of competence genes.

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