Single-Chain Antibody Displayed on a Recombinant Measles Virus Confers Entry through the Tumor-Associated Carcinoembryonic Antigen

Hammond, Anthea L.; Plemper, Richard K.; Zhang, Jie; Schneider, Urs; Russell, Stephen J.; Cattaneo, Roberto

doi:10.1128/jvi.75.5.2087-2096.2001

Cited by 112 publications

(76 citation statements)

References 34 publications

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“…1A). Targeting of MC38cea cells 19 was achieved using a single chain antibody (scAb) against CEA 20 and the STAR system. 21 The MeVac vector encoding eGFP and harboring the fully retargeted H protein (Hbl-aCEA) productively infected the producer Vero-aHis and target MC38cea cells, as indicated by syncytia formation, but not the parental Vero and MC38 cells, respectively (Fig.…”

Section: Targeted Immunomodulatory Oncolytic Measles Virus Vectorsmentioning

confidence: 99%

Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation

et al. 2017

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Combination of oncolytic virotherapy with immunomodulators is emerging as a promising therapeutic strategy for numerous tumor entities. In this study, we developed measles Schwarz vaccine strain vectors encoding immunomodulators to support different phases in the establishment of antitumor immune responses. Therapeutic efficacy of the novel vectors was evaluated in the immunocompetent MC38cea tumor model. We identified vectors encoding an IL-12 fusion protein (MeVac FmIL-12) and an antibody against PD-L1 (MeVac anti-PD-L1), respectively, as the most effective. Treatment of established tumors with MeVac FmIL-12 achieved 90% complete remissions. Profiling of the tumor immune microenvironment revealed activation of a type 1 T helper cell-directed response, with MeVac FmIL-12 ensuring potent early natural killer and effector T cell activation as well as upregulation of the effector cytokines IFN-g and TNF-a. CD8C T cells were found to be essential for the therapeutic efficacy of MeVac FmIL-12. Results of this study present MeVac FmIL-12 as a novel approach for targeted IL-12 delivery and elucidate mechanisms of successful immunovirotherapy.

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Section: Targeted Immunomodulatory Oncolytic Measles Virus Vectorsmentioning

confidence: 99%

Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation

et al. 2017

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“…1 Studies are ongoing using adenovirus, 2,3 herpes simplex virus, 4 reovirus, 5 Newcastle disease virus, 6 vaccinia virus, 7 poliovirus, 8 VSV and measles virus. 9,10 Efficacy and safety are the crucial issues. VSV is an excellent candidate for development as an oncolytic virus because it is an efficient cell killer that does not produce serious human disease.…”

Section: Introductionmentioning

confidence: 99%

Recombinant vesicular stomatitis virus targeted to Her2/neu combined with anti-CTLA4 antibody eliminates implanted mammary tumors

et al. 2008

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Vesicular stomatitis virus (VSV) is being developed for cancer therapy. We created a recombinant replicating VSV (rrVSV) that preferentially infected Her2/neu expressing breast cancer cells. We now used this rrVSV to treat macroscopic peritoneal tumor implants of a mouse mammary tumor cell line stably transfected to express Her2/neu. rrVSV therapy alone prolonged survival but did not cure any animals. rrVSV therapy combined with antibody to TGFb or antibody to IL-10 receptor (IL-10R) each produced cure in one of six animals. Strikingly, rrVSV therapy combined with anti-CTLA4 monoclonal antibody (MAb) produced cure in four of five animals. Anti-CTLA4 MAb was only effective when administered within one day of rrVSV therapy. Cure required CD4 T-cells early (o7 days) and late (47 days) after rrVSV therapy whereas CD8 T-cells were required only late (47 days) after rrVSV therapy. Surviving animals were resistant to re-challenge with D2F2/E2 suggesting a memory immune response. Histopathologic analysis demonstrated a dense inflammatory infiltrate of tumor nodules within days of therapy and foamy histiocytes replacing the tumor nodules 2 weeks following therapy. These studies demonstrate that targeted rrVSV combined with anti-CTLA4 MAb can eliminate established macroscopic tumor implants by eliciting an anti-tumor CD4 and CD8 T-cell immunologic response.

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“…Attenuated measles viruses were recently reported to have potent and selective oncolytic activity against human tumor xenografts [13][14][15][16] and the host range properties of the virus were successfully modified by display of polypeptide ligands at the C-terminus of the H protein. [17][18][19][20] In light of its dual role in mediating both virus-cell and cell-cell fusion, the H protein of measles virus therefore provided an attractive platform for display of TCR to determine the feasibility of TCR-directed membrane fusion.…”

Section: Introductionmentioning

confidence: 99%

Targeting virus entry and membrane fusion through specific peptide/MHC complexes using a high-affinity T-cell receptor

et al. 2004

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The T-cell receptor (TCR) determines the specificity of T-cell recognition by binding to peptide fragments of intracellular proteins presented at the cell surface in association with molecules of the major histocompatibility complex (MHC). Engagement of the TCR by its cognate peptide/MHC ligand, with appropriate co-stimulatory signals, leads to activation of T-cell effector functions. Here we show that the attachment proteins of attenuated measles viruses, engineered to display a high-affinity single-chain TCR (scTCR), can recognize and bind to specific peptide-MHC complexes and thereby mediate targeted virus-cell entry and cell-to-cell fusion. Using the 2C TCR and its peptide/MHC ligand (SIYRYYGL/mouse K b ), we show that a scTCR grafted onto the measles virus H protein confers new specificity to virus entry and cell fusion. The efficiency of TCR-mediated virus entry was dependent on the number of peptide/MHC complexes expressed on the target cells, increasing progressively above densities higher than 2500 complexes per cell. This work introduces a new paradigm for targeting virus entry and membrane fusion by extending the repertoire of targets to specific peptide-MHC ligands and offering a novel quantitative readout for the cellular expression of peptide-MHC complexes.

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Single-Chain Antibody Displayed on a Recombinant Measles Virus Confers Entry through the Tumor-Associated Carcinoembryonic Antigen

Cited by 112 publications

References 34 publications

Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation

Oncolytic measles virus encoding interleukin-12 mediates potent antitumor effects through T cell activation

Recombinant vesicular stomatitis virus targeted to Her2/neu combined with anti-CTLA4 antibody eliminates implanted mammary tumors

Targeting virus entry and membrane fusion through specific peptide/MHC complexes using a high-affinity T-cell receptor

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