Cited by 361
Johannes Gutenberg University Mainz
Publishes on Immunotherapy and Immune Responses, CAR-T cell therapy research, Monoclonal and Polyclonal Antibodies Research. 4 papers and 868 citations.
Add your photo, update your bio, and get notified when your ranking changes.
Adoptive transfer of T lymphocytes is a promising treatment for a variety of malignancies but often not feasible due to difficulties generating T cells that are reactive with the targeted antigen from patients. To facilitate rapid generation of cells for therapy, T cells can be programmed with genes encoding the alpha and beta chains of an antigen-specific T-cell receptor (TCR). However, such exogenous alpha and beta chains can potentially assemble as pairs not only with each other but also with endogenous TCR alpha and beta chains, thereby generating alphabetaTCR pairs of unknown specificity as well as reducing the number of exogenous matched alphabetaTCR pairs at the cell surface. We demonstrate that introducing cysteines into the constant region of the alpha and beta chains can promote preferential pairing with each other, increase total surface expression of the introduced TCR chains, and reduce mismatching with endogenous TCR chains. This approach should improve both the efficacy and safety of ongoing efforts to use TCR transfer as a strategy to generate tumor-reactive T cells.
Many strategies for redirecting the tropism of murine Moloney leukemia virus (MMLV) have been described. Preformed virion-liposome complexes, termed virosomes, have been reported to be relatively stable. Virosomes mediate envelope-independent transduction that allows efficient superinfection of resistant cell lines; however, virosome-mediated transduction behaves in a non-target-specific manner. We developed a novel method using antibodies to direct MMLV to vascular endothelium. We have given the term immunovirosomes to the complexes formed between viruses, liposomes, and antibodies. These immunovirosomes improve the transduction efficiency of the viruses and alter their tropism. We have shown improved transduction when immunovirosomes were targeted at the endocytic receptors CD71 and CD62E/P and rather less good delivery when targeted at CD106. The enhancement of the transduction efficiency was transient, however, suggesting that rerouting the entry pathway of viruses alters the expression properties of the viruses.