7 results on '"Scarselli, Elisa"'
Search Results
2. Adenoviral-based vaccine promotes neoantigen-specific CD8+ T cell stemness and tumor rejection.
- Author
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D'Alise, Anna Morena, Brasu, Nadia, De Intinis, Carlo, Leoni, Guido, Russo, Valentina, Langone, Francesca, Baev, Denis, Micarelli, Elisa, Petiti, Luca, Picelli, Simone, Fakih, Marwan, Le, Dung T., Overman, Michael J., Shields, Anthony F., Pedersen, Katrina S., Shah, Manish A., Mukherjee, Sarbajit, Faivre, Thea, Delaite, Patricia, and Scarselli, Elisa
- Subjects
T cells ,T cell receptors ,COMBINED vaccines ,IMMUNOLOGIC memory ,CANCER vaccines ,HOMINIDS ,CYTOTOXIC T cells - Abstract
Upon chronic antigen exposure, CD8
+ T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+ T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)–vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti–programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+ T cells over αPD-1 monotherapy, with an accumulation of Tcf1+ stem-like progenitors in draining lymph nodes and effector CD8+ T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+ T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors. Immunotherapy that is not monkeying around: Adenoviral vaccines encoding for tumor neoantigens have shown promise treating solid tumors when combined with anti–programmed cell death protein 1 (αPD-1) preclinically; however, the mechanism is not well understood. To elucidate this, Chen et al. generated Great Ape adenovirus (GAd) vaccines and treated tumor-bearing mice in combination with αPD-1 to elicit an accumulation of Tcf1+ stem-like CD8+ T cell progenitors, improving immunogenicity and antitumor efficacy. In addition, they performed a first-in-human trial on patients with metastatic mismatch repair–deficient tumors and saw a clinical response, suggesting this as a promising therapy to overcome resistance to αPD-1 treatment. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
3. Chimpanzee adenovirus– and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults
- Author
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Green, Christopher A., primary, Scarselli, Elisa, additional, Sande, Charles J., additional, Thompson, Amber J., additional, de Lara, Catherine M., additional, Taylor, Kathryn S., additional, Haworth, Kathryn, additional, Del Sorbo, Mariarosaria, additional, Angus, Brian, additional, Siani, Loredana, additional, Di Marco, Stefania, additional, Traboni, Cinzia, additional, Folgori, Antonella, additional, Colloca, Stefano, additional, Capone, Stefania, additional, Vitelli, Alessandra, additional, Cortese, Riccardo, additional, Klenerman, Paul, additional, Nicosia, Alfredo, additional, and Pollard, Andrew J., additional
- Published
- 2015
- Full Text
- View/download PDF
4. Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections
- Author
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Taylor, Geraldine, primary, Thom, Michelle, additional, Capone, Stefania, additional, Pierantoni, Angiolo, additional, Guzman, Efrain, additional, Herbert, Rebecca, additional, Scarselli, Elisa, additional, Napolitano, Federico, additional, Giuliani, Alessandro, additional, Folgori, Antonella, additional, Colloca, Stefano, additional, Cortese, Riccardo, additional, Nicosia, Alfredo, additional, and Vitelli, Alessandra, additional
- Published
- 2015
- Full Text
- View/download PDF
5. Adenoviral-based vaccine promotes neoantigen-specific CD8+T cell stemness and tumor rejection
- Author
-
D’Alise, Anna Morena, Brasu, Nadia, De Intinis, Carlo, Leoni, Guido, Russo, Valentina, Langone, Francesca, Baev, Denis, Micarelli, Elisa, Petiti, Luca, Picelli, Simone, Fakih, Marwan, Le, Dung T., Overman, Michael J., Shields, Anthony F., Pedersen, Katrina S., Shah, Manish A., Mukherjee, Sarbajit, Faivre, Thea, Delaite, Patricia, Scarselli, Elisa, and Pace, Luigia
- Abstract
Upon chronic antigen exposure, CD8+T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)–vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti–programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+T cells over αPD-1 monotherapy, with an accumulation of Tcf1+stem-like progenitors in draining lymph nodes and effector CD8+T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.
- Published
- 2022
- Full Text
- View/download PDF
6. Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections
- Author
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Elisa Scarselli, Federico Napolitano, Efrain Guzman, Stefania Capone, Geraldine Taylor, Riccardo Cortese, Alessandra Vitelli, Stefano Colloca, Alessandro Giuliani, Antonella Folgori, Rebecca Herbert, Alfredo Nicosia, Angiolo Pierantoni, Michelle Thom, Taylor, Geraldine, Thom, Michelle, Capone, Stefania, Pierantoni, Angiolo, Guzman, Efrain, Herbert, Rebecca, Scarselli, Elisa, Napolitano, Federico, Giuliani, Alessandro, Folgori, Antonella, Colloca, Stefano, Cortese, Riccardo, Nicosia, Alfredo, and Vitelli, Alessandra
- Subjects
Modified vaccinia Ankara ,Cellular immunity ,viruses ,Genetic Vectors ,Immunization, Secondary ,Respiratory Syncytial Virus, Bovine ,Respiratory Syncytial Virus Infections ,Biology ,Virus ,Principal Component Analysi ,Antibody Specificity ,Immunity ,Lower respiratory tract infection ,Respiratory Syncytial Virus Vaccines ,medicine ,Animals ,Humans ,Sigmodontinae ,Lung ,Respiratory Syncytial Virus Infection ,Immunity, Cellular ,Principal Component Analysis ,Animal ,Medicine (all) ,Vaccination ,Respiratory disease ,General Medicine ,medicine.disease ,Virology ,Treatment Outcome ,Respiratory Syncytial Virus Vaccine ,Respiratory Syncytial Virus, Human ,Immunology ,Cattle ,Genetic Vector ,Human - Abstract
Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man.
- Published
- 2015
7. Adenoviral-based vaccine promotes neoantigen-specific CD8 + T cell stemness and tumor rejection.
- Author
-
D'Alise AM, Brasu N, De Intinis C, Leoni G, Russo V, Langone F, Baev D, Micarelli E, Petiti L, Picelli S, Fakih M, Le DT, Overman MJ, Shields AF, Pedersen KS, Shah MA, Mukherjee S, Faivre T, Delaite P, Scarselli E, and Pace L
- Subjects
- Adenoviridae, Animals, Antigens, Neoplasm metabolism, Humans, Mice, Receptors, Antigen, T-Cell metabolism, CD8-Positive T-Lymphocytes, Neoplasms metabolism
- Abstract
Upon chronic antigen exposure, CD8
+ T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+ T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)-vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti-programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+ T cells over αPD-1 monotherapy, with an accumulation of Tcf1+ stem-like progenitors in draining lymph nodes and effector CD8+ T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+ T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.- Published
- 2022
- Full Text
- View/download PDF
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