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Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Highly efficient and selective CAR-gene transfer using CD4- and CD8-targeted lentiviral vectors. Cell type-specific targeting with surface-engineered lentiviral vectors co-displaying OKT3 antibody and fusogenic molecule. Targeted transduction via CD4 by a lentiviral vector uses a clathrin-mediated entry pathway. Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection. Lentiviral vector interactions with the host cell. Engineering HIV-specific immunity with chimeric antigen receptors. Multispecific anti-HIV duoCAR-T cells display broad in vitro antiviral activity and potent in vivo elimination of HIV-infected cells in a humanized mouse model. Human lymphoid and myeloid cell development in NOD/LtSz- scid IL2Rγ null mice engrafted with mobilized human hemopoietic stem cells. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chain null mice. Complete reconstitution of human lymphocytes from cord blood CD34 + cells using the NOD/SCID/γcnull mice model. NOD/SCID/γcnull mouse: an excellent recipient mouse model for engraftment of human cells. New generation humanized mice for virus research: comparative aspects and future prospects. CAR T cells beyond cancer: hope for immunomodulatory therapy of infectious diseases. Genetic in vivo engineering of human T lymphocytes in mouse models. Receptor-targeted Nipah virus glycoproteins improve cell-type selective gene delivery and reveal a preference for membrane-proximal cell attachment. CD8-specific DARPins improve selective gene delivery into human and primate T lymphocytes. Exclusive transduction of human CD4 + T cells upon systemic delivery of CD4-targeted lentiviral vectors. T-cell receptor gene transfer exclusively to human CD8 + cells enhances tumor cell killing. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 53, 52–57 (2010). Environmental risk assessment for medicinal products containing genetically modified organisms.

Targeted cell entry of lentiviral vectors. Surface-engineered viral vectors for selective and cell type-specific gene delivery. In vivo generation of CAR T cells selectively in human CD4 + lymphocytes. In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome. In vivo generated human CAR T cells eradicate tumor cells. Surface-engineered lentiviral vectors for selective gene transfer into subtypes of lymphocytes. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Paths to stemness: building the ultimate antitumour T cell. Electroporation enables plasmid vaccines to elicit CD8 + T cell responses in the absence of CD4 + T cells. Optimized DNA electroporation for primary human T cell engineering. Vectofusin-1 improves transduction of primary human cells with diverse retroviral and lentiviral pseudotypes, enabling robust, automated closed-system manufacturing. We also discuss how the protocol can be easily adapted to use LVs targeted to other types of receptors and/or for delivery of other genes of interest. By closely following the protocol, sufficient vector stock for the genetic manipulation of 10–15 humanized mice is obtained. A few weeks after administration, ~10% of the targeted T-cell subtype can be expected to have converted to CAR T cells. Conversion of the targeted cell type is monitored by PCR and flow cytometry of blood samples.

Perian biosciences how to#

We also describe how to humanize immunodeficient mice with hematopoietic stem cells (which takes 12–16 weeks) and precondition (over 5 d) and administer the vector stocks. Here, we provide detailed protocols for the generation of CD4- and CD8-targeted LVs (which takes ~9 d in total). For example, T cells in humanized mouse models can be modified by lentiviral vectors (LVs) targeted to human T-cell markers to enable them to express chimeric antigen receptors (CARs). Receptor targeting of vector particles is a key technology to enable cell type–specific in vivo gene delivery.