PAVE
A nanovaccine Approach for the treatment of Pancreatic Cancer
Main Achievements of PAVE
The project generated multicomponent nanovaccines targeting tumour associated antigens by encapsulating one of the following peptides i) NY-ESO1, ii) four sequences of mesothelin (MSLN), and iii) KRAS peptide, as well as different adjuvants such as the TLR3 agonist Poly(I:C; pIC) and the dual TLR7/8 activator Resiquimod (R848). Covalent attachment of polyethylene glycol chains increased the solubility, bulk amount, and recovery of most peptides. Several of the synthesized peptides were encapsulated into polymer PLGA-NPs, that were coated with chitosan to prevent aggregation and increase the affinity to tumour cells. Nanovaccines were partly labeled with fluorescent dyes, for visual tracking in both in vitro as well as in vivo assays. These vaccines were designed to stimulate a robust immune response, particularly by activating T-cells against PDAC cells.
Recognizing the limitations of existing preclinical models, PAVE developed new models, including a porcine (pig) model that replicates human PDAC more accurately than traditional mouse models. This "oncopig" with specific genetic mutations relevant to PDAC, provides a valuable tool for testing the efficacy of new therapies. In addition, PAVE succeeded in developing a toolbox of pig-specific immunology reagents and assays including bioactive immune proteins, cloned cytokine and chemokine proteins, and monoclonal antibodies to the proteins and their receptors for the porcine model.
PAVE researchers developed several innovative imaging tools, such as near-infrared fluorescent biosensors, transgenic mice with bioluminescent and fluorescent gene reporters, and optoacoustic imaging techniques. These tools enable for example real-time tracking of vaccine biodistribution, T-cell activation, and tumour progression in vivo, enhancing the ability to monitor treatment responses to optimize the therapeutic strategy.
The project made significant progress in understanding the immunosuppressive nature of the PDAC tumour microenvironment (TME). This included the identification of immunoregulatory genes (IRGs) whose knockdown improved T-cell mediated tumor killing, the characterization of the heterogeneity of cancer associated fibroblasts (CAFs) in human PDAC, and the development of a novel platform for constructing immune component-based antigens targeting key PDAC proteins such as mesothelin and KRAS.
Research on the role of extracellular vesicles (EVs) in PDAC revealed their strong thrombotic potential, which could contribute to the understanding of the high incidence of thrombosis in PDAC patients. This finding opens the door to use EVs as biomarkers for assessing thrombosis risk in these patients.
PAVE demonstrated that the mesothelin-based nanovaccines could effectively reduce tumor growth and metastasis in PDAC mouse models. These nanovaccines further showed potential synergistic effects when combined with other therapies, such as immune checkpoint inhibitors and conventional chemotherapy in human PDAC organoid co-cultures. Given age-related immune decline, the project also investigated whether senolysis before vaccination could enhance immune responses in aged mice and whether there is an age-related difference in immune response to the MSLN nanovaccine. No significant difference was observed between young and old mice in their response.
The project also advanced methods for analyzing tumor heterogeneity using single-cell data, which is crucial for understanding the complex interactions of tumour, immune cells and fibroblasts within the TME and for identifying new therapeutic targets.
Publications
Author(s): Giuseppina Roscigno, Iolanda Scognamiglio, Francesco Ingenito, Rosario Vincenzo Chianese, Francesco Palma, Alan Chan, Gerolama Condorelli
Published in: Cancers, Issue 12/12, 2020, Page(s) 3744, ISSN 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers12123744
Author(s): Menevse, Ayse Nur; Ammer, Laura-Marie; Vollmann-Zwerenz, Arabel; Kupczyk, Marcell; Lorenz, Julia; Weidner, Lorraine; Hussein, Abir; Sax, Julian; Mülbauer, Jasmin; Heuschneider, Nicole; Rohrmus, Celine; Mai, Laura S; Jachnik, Birgit; Stamova, Slava; Volpin, Valentina; Durst, Franziska C; Sorrentino, Antonio; Xydia, Maria; Milenkovic, Vladimir M; Bader, Stefanie; Braun, Frank K; Wetzel, Christian;
Published in: Acta neuropathologica communications., Issue 11(1), 2023, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-023-01550-9
Tea Bags for Fmoc Solid-Phase Peptide Synthesis: An Example of Circular Economy
Author(s): Fanny Guzmán, Adriana Gauna, Tanya Roman, Omar Luna, Claudio Álvarez, Claudia Pareja-Barrueto, Luis Mercado, Fernando Albericio, Constanza Cárdenas
Published in: Molecules, Issue 26/16, 2021, Page(s) 5035, ISSN 1420-3049
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/molecules26165035
miR-34c-3p targets CDK1 a synthetic lethality partner of KRAS in non-small cell lung cancer
Author(s): Francesco Palma, Alessandra Affinito, Silvia Nuzzo, Giuseppina Roscigno, Iolanda Scognamiglio, Francesco Ingenito, Lola Martinez, Monica Franzese, Mario Zanfardino, Andrea Soricelli, Alfonso Fiorelli, Gerolama Condorelli, Cristina Quintavalle
Published in: Cancer Gene Therapy, 2020, ISSN 0929-1903
Publisher: Nature Publishing Group
DOI: 10.1038/s41417-020-00224-1
The Missing Link: Cre Pigs for Cancer Research
Author(s): Daniela Kalla, Krzysztof Flisikowski, Kaiyuan Yang, Laura Beltran Sangüesa, Mayuko Kurome, Barbara Kessler, Valeri Zakhartchenko, Eckhard Wolf, Heiko Lickert, Dieter Saur, Angelika Schnieke, Tatiana Flisikowska
Published in: Frontiers in Oncology, Issue 11, 2021, ISSN 2234-943X
Publisher: Frontiers Media S. A.
DOI: 10.3389/fonc.2021.755746
Author(s): Antonio Sorrentino, Ayse Nur Menevse, Tillmann Michels, Valentina Volpin, Franziska Christine Durst, Julian Sax, Maria Xydia, Abir Hussein, Slava Stamova, Steffen Spoerl, Nicole Heuschneider, Jasmin Muehlbauer, Katharina Marlene Jeltsch, Anchana Rathinasamy, Melanie Werner-Klein, Marco Breinig, Damian Mikietyn, Christian Kohler, Isabel Poschke, Sabrina Purr, Olivia Reidell, Catarina Martins Freire
Published in: Journal for immunotherapy of cancer., Issue 10(5), 2022, ISSN 2051-1426
Publisher: BMJ Publishing Group Ltd.
DOI: 10.1136/jitc-2021-004258
Author(s): Fernanda Ramos-Gomes, Nathalia Ferreira, Frauke Alves, M Andrea Markus
Published in: Bio-protocol., Issue 12(2), 2022, ISSN 2331-8325
Publisher: Sunnyvale, CA, USA : Bio-protocol LLC, [2011]-
DOI: 10.21769/bioprotoc.4293
Emerging tools for bioluminescence imaging
Author(s): Giorgia Zambito, Chintan Chawda, Laura Mezzanotte
Published in: Current Opinion in Chemical Biology, Issue 63, 2021, Page(s) 86-94, ISSN 1367-5931
Publisher: Elsevier BV
DOI: 10.1016/j.cbpa.2021.02.005
Author(s): Hayden Pearce; Wayne Croft; Sandra Margielewska-Davies; Lindsay Lim; Samantha M Nicol; Fouzia Zayou; Daniel Blakeway; Francesca Marcon; Sarah Powell-Brett; Brinder Mahon; Reena Merard; Jianmin Zuo; Gary Middleton; Keith Roberts; Rachel M Brown; Paul Moss
Published in: eLife., Issue 12, 2023, ISSN 2050-084X
Publisher: eLife Sciences Publications
DOI: 10.7554/elife.86125
Author(s): Giuseppina Roscigno, Assunta Cirella, Alessandra Affinito, Cristina Quintavalle, Iolanda Scognamiglio, Francesco Palma, Francesco Ingenito, Silvia Nuzzo, Francesca De Micco, Antonio Cuccuru, Renato Thomas, Gerolama Condorelli
Published in: International Journal of Molecular Sciences, Issue 21/7, 2020, Page(s) 2313, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms21072313
Ex vivo Live Cell Imaging of Nanoparticle-Cell Interactions in the Mouse Lung
Author(s): Fernanda Ramos-Gomes, Nathalia Ferreira, Alexander Kraupner, Frauke Alves, M. Andrea Markus
Published in: Frontiers in Bioengineering and Biotechnology, Issue 8, 2020, ISSN 2296-4185
Publisher: Frontiers Media SA
DOI: 10.3389/fbioe.2020.588922
Author(s): Krog, R.T.; Miranda, N.F.C.C. de; Vahrmeijer, A.L.; Kooreman, N.G.
Published in: Cancer, Issue 13(22), 5789;, 2021, Page(s) 5789, ISSN 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/cancers13225789
Identification of a novel RNA aptamer that selectively targets breast cancer exosomes
Author(s): Carla Lucia Esposito, Cristina Quintavalle, Francesco Ingenito, Deborah Rotoli, Giuseppina Roscigno, Silvia Nuzzo, Renato Thomas, Silvia Catuogno, Vittorio de Franciscis, Gerolama Condorelli
Published in: Molecular Therapy - Nucleic Acids, 2021, ISSN 2162-2531
Publisher: Nature Publishing Group
DOI: 10.1016/j.omtn.2021.01.012
scMoC: single-cell multi-omics clustering
Author(s): Mostafa Eltager, Tamim Abdelaal, Ahmed Mahfouz, Marcel J. T. Reinders
Published in: Bioinformatics Advances, 2022 Feb 15;2(1):vbac011
Publisher: Oxford University Press : International Society for Computational Biology,
DOI: 10.1093/bioadv/vbac011
Benchmarking variational AutoEncoders on cancer transcriptomics data
Author(s): Eltager M, Abdelaal T, Charrout M, Mahfouz A, Reinders MJT, Makrodimitris S.
Published in: PLoS One. 2023 Oct 5;18(10):e0292126.
Publisher: San Francisco, CA : Public Library of Science
10.1371/journal.pone.0292126
Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer
Author(s): Carla Lucia, Scognamiglio I, Cocca L, Puoti I, Palma F, Ingenito F, Quintavalle C, Affinito A, Roscigno G, Nuzzo S, Chianese RV, Belli S, Thomas G, Schomann T, Chan A, Stoppelli MP, Condorelli G
Published in: Mol Ther Nucleic Acids. 2022 Feb 22;28:17-31
Publisher: New York, NY : Nature Pub. Group
DOI: 10.1016/j.omtn.2022.02.013
Author(s): Ozmen Cobanoglu, Lou Delval, Daniele Ferrari, Lucie Deruyter, Séverine Heumel, Isabelle Wolowczuk, Abir Hussein, Ayse Nur Menevse, David Bernard, Philip Beckhove, Frauke Alves, François Trottein
Published in: Aging Cell. 2023 Dec;22(12):e14007
Publisher: Oxford, UK : Blackwell Pub.
DOI: 10.1111/acel.14007
Amide Formation: Choosing the Safer Carbodiimide in Combination with OxymaPure to Avoid HCN Release.
Author(s): Srinivasa Rao Manne, Omar Luna, Gerardo A Acosta, Miriam Royo, Ayman El-Faham, Gyorgy Orosz, Beatriz G de la Torre, Fernando Albericio
Published in: Org Lett. 2021 Sep 3;23(17):6900-6904
Publisher: Washington, DC : American Chemical Society
DOI: 10.1021/acs.orglett.1c02466
Author(s): M Andrea Markus, Daniele P Ferrari, Frauke Alves, Fernanda Ramos-Gomes
Published in: Biomed Opt Express. 2023 Jul 10;14(8):3988-4002
Publisher: Washington, DC : Optical Society of America
DOI: 10.1364/BOE.488453
THIS PROJECT HAS RECEIVED FUNDING FROM THE EUROPEAN UNION’S HORIZON 2020 RESEARCH AND INNOVATION PROGRAMME UNDER THE MARIE SKŁODOWSKA-CURIE GRANT AGREEMENT NO 861190
© Urheberrecht. Alle Rechte vorbehalten.
Wir benötigen Ihre Zustimmung zum Laden der Übersetzungen
Wir nutzen einen Drittanbieter-Service, um den Inhalt der Website zu übersetzen, der möglicherweise Daten über Ihre Aktivitäten sammelt. Bitte überprüfen Sie die Details in der Datenschutzerklärung und akzeptieren Sie den Dienst, um die Übersetzungen zu sehen.