دورية أكاديمية
Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma.
| العنوان: | Vaccination with Designed Neopeptides Induces Intratumoral, Cross-reactive CD4+ T-cell Responses in Glioblastoma. |
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| المؤلفون: | Wang J; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, P.R. China., Weiss T; Laboratory of Molecular Neuro-Oncology, Department of Neurology and Brain Tumor Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Neidert MC; Clinical Neuroscience Center and Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.; Department of Neurosurgery, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Toussaint NC; NEXUS Personalized Health Technologies, ETH Zurich, Schlieren, Switzerland.; Swiss Institute of Bioinformatics, Zurich, Switzerland., Naghavian R; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Sellés Moreno C; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Foege M; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Tomas Ojer P; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Medici G; Clinical Neuroscience Center and Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Jelcic I; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Schulz D; Department of Quantitative Biomedicine, University of Zürich, Zurich, Switzerland.; Institute of Molecular Life Sciences, University of Zürich, Zurich, Switzerland., Rushing E; Institute of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Dettwiler S; Institute of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Schrörs B; TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg-University gGmbH, Mainz, Germany., Shin JH; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, Maryland., McKay R; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, Maryland., Wu CJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts.; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts., Lutterotti A; Cellerys AG, Wagnerstrasse 11, Zürich, Switzerland., Sospedra M; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Moch H; Institute of Pathology and Molecular Pathology, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Greiner EF; Cedrus Therapeutics, Wilmington, Delaware., Bodenmiller B; Department of Quantitative Biomedicine, University of Zürich, Zurich, Switzerland.; Institute of Molecular Life Sciences, University of Zürich, Zurich, Switzerland., Regli L; Clinical Neuroscience Center and Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Weller M; Laboratory of Molecular Neuro-Oncology, Department of Neurology and Brain Tumor Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Roth P; Laboratory of Molecular Neuro-Oncology, Department of Neurology and Brain Tumor Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Martin R; Neuroimmunology and MS Research, Neurology Clinic, University Hospital Zurich, University of Zurich, Zurich, Switzerland. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2022 Dec 15; Vol. 28 (24), pp. 5368-5382. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | CD4-Positive T-Lymphocytes* , Glioblastoma*/genetics , Glioblastoma*/therapy, Humans ; Neoplasm Recurrence, Local ; Lymphocytes, Tumor-Infiltrating ; Receptors, Antigen, T-Cell/genetics ; Vaccination ; Peptides ; Amino Acids ; CD8-Positive T-Lymphocytes |
| مستخلص: | Purpose: The low mutational load of some cancers is considered one reason for the difficulty to develop effective tumor vaccines. To overcome this problem, we developed a strategy to design neopeptides through single amino acid mutations to enhance their immunogenicity. Experimental Design: Exome and RNA sequencing as well as in silico HLA-binding predictions to autologous HLA molecules were used to identify candidate neopeptides. Subsequently, in silico HLA-anchor placements were used to deduce putative T-cell receptor (TCR) contacts of peptides. Single amino acids of TCR contacting residues were then mutated by amino acid replacements. Overall, 175 peptides were synthesized and sets of 25 each containing both peptides designed to bind to HLA class I and II molecules applied in the vaccination. Upon development of a tumor recurrence, the tumor-infiltrating lymphocytes (TIL) were characterized in detail both at the bulk and clonal level. Results: The immune response of peripheral blood T cells to vaccine peptides, including natural peptides and designed neopeptides, gradually increased with repetitive vaccination, but remained low. In contrast, at the time of tumor recurrence, CD8+ TILs and CD4+ TILs responded to 45% and 100%, respectively, of the vaccine peptides. Furthermore, TIL-derived CD4+ T-cell clones showed strong responses and tumor cell lysis not only against the designed neopeptide but also against the unmutated natural peptides of the tumor. Conclusions: Turning tumor self-peptides into foreign antigens by introduction of designed mutations is a promising strategy to induce strong intratumoral CD4+ T-cell responses in a cold tumor like glioblastoma. (©2022 The Authors; Published by the American Association for Cancer Research.) |
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| المشرفين على المادة: | 0 (Receptors, Antigen, T-Cell) 0 (Peptides) 0 (Amino Acids) |
| تواريخ الأحداث: | Date Created: 20221013 Date Completed: 20221216 Latest Revision: 20230122 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9751771 |
| DOI: | 10.1158/1078-0432.CCR-22-1741 |
| PMID: | 36228153 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-22-1741 |