دورية أكاديمية
Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma.
| العنوان: | Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. |
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| المؤلفون: | Mueller S; Department of Neurology.; Department of Neurosurgery and.; Department of Pediatrics, UCSF, San Francisco, California, USA.; Children's University Hospital Zurich, Switzerland., Taitt JM; Department of Neurosurgery and., Villanueva-Meyer JE; Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA., Bonner ER; Children's National Medical Center, Washington, DC, USA., Nejo T; Department of Neurosurgery and., Lulla RR; Division of Pediatric Hematology/Oncology, Hasbro Children's Hospital, Department of Pediatrics, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA., Goldman S; Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Banerjee A; Department of Neurosurgery and.; Department of Pediatrics, UCSF, San Francisco, California, USA., Chi SN; Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Whipple NS; Division of Hematology/Oncology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA., Crawford JR; Department of Neurosciences and Pediatrics, UCSD and Rady Children's Hospital, San Diego, California, USA., Gauvain K; St. Louis Children's Hospital, Washington University in St. Louis, St. Louis, Missouri, USA., Nazemi KJ; Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon, USA., Watchmaker PB; Department of Neurosurgery and., Almeida ND; The George Washington University School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia, USA., Okada K; Department of Neurosurgery and., Salazar AM; Oncovir Inc., Washington, DC, USA., Gilbert RD; Department of Neurosurgery and., Nazarian J; Children's University Hospital Zurich, Switzerland.; Children's National Medical Center, Washington, DC, USA., Molinaro AM; Department of Neurosurgery and., Butterfield LH; Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.; Department of Microbiology and Immunology, UCSF, San Francisco, California, USA., Prados MD; Department of Neurosurgery and.; Department of Pediatrics, UCSF, San Francisco, California, USA., Okada H; Department of Neurosurgery and.; Parker Institute for Cancer Immunotherapy, San Francisco, California, USA.; Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California, USA. |
| المصدر: | The Journal of clinical investigation [J Clin Invest] 2020 Dec 01; Vol. 130 (12), pp. 6325-6337. |
| نوع المنشور: | Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation Original Publication: New Haven [etc.] American Society for Clinical Investigation. |
| مواضيع طبية MeSH: | Brain Stem Neoplasms*/genetics , Brain Stem Neoplasms*/immunology , Brain Stem Neoplasms*/therapy , Cancer Vaccines*/administration & dosage , Cancer Vaccines*/genetics , Cancer Vaccines*/immunology , Flow Cytometry* , Glioma*/genetics , Glioma*/immunology , Glioma*/therapy , Histones*/genetics , Histones*/immunology , Mutation, Missense* , Neoplasm Proteins*/genetics , Neoplasm Proteins*/immunology, CD8-Positive T-Lymphocytes/*immunology , Immunity, Cellular/*drug effects, Adolescent ; Adult ; Amino Acid Substitution ; Child ; Child, Preschool ; Female ; Humans ; Immunity, Cellular/genetics ; Male |
| مستخلص: | BACKGROUNDPatients with diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, with HLA-A*02.01+ and H3.3K27M+ status were enrolled in stratum A (DIPG) or stratum B (nonpontine DMG). Vaccine was administered in combination with polyinosinic-polycytidylic acid-poly-I-lysine carboxymethylcellulose (poly-ICLC) every 3 weeks for 8 cycles, followed by once every 6 weeks. Immunomonitoring and imaging were performed every 3 months. Imaging was centrally reviewed. Immunological responses were assessed in PBMCs using mass cytometry.RESULTSA total of 19 patients were enrolled in stratum A (median age,11 years) and 10 in stratum B (median age, 13 years). There were no grade-4 treatment-related adverse events (TRAEs). Injection site reaction was the most commonly reported TRAE. Overall survival (OS) at 12 months was 40% (95% CI, 22%-73%) for patients in stratum A and 39% (95% CI, 16%-93%) for patients in stratum B. The median OS was 16.1 months for patients who had an expansion of H3.3K27M-reactive CD8+ T cells compared with 9.8 months for their counterparts (P = 0.05). Patients with DIPG with below-median baseline levels of myeloid-derived suppressor cells had prolonged OS compared with their counterparts (P < 0.01). Immediate pretreatment dexamethasone administration was inversely associated with H3.3K27M-reactive CD8+ T cell responses.CONCLUSIONAdministration of the H3.3K27M-specific vaccine was well tolerated. Patients with H3.3K27M-specific CD8+ immunological responses demonstrated prolonged OS compared with nonresponders.TRIAL REGISTRATIONClinicalTrials.gov NCT02960230.FUNDINGThe V Foundation, the Pacific Pediatric Neuro-Oncology Consortium Foundation, the Pediatric Brain Tumor Foundation, the Mithil Prasad Foundation, the MCJ Amelior Foundation, the Anne and Jason Farber Foundation, Will Power Research Fund Inc., the Isabella Kerr Molina Foundation, the Parker Institute for Cancer Immunotherapy, and the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R35NS105068). |
| التعليقات: | Erratum in: J Clin Invest. 2022 Jun 15;132(12):. (PMID: 35703183) |
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| معلومات مُعتمدة: | P30 CA047904 United States CA NCI NIH HHS; P30 DK063720 United States DK NIDDK NIH HHS; R35 NS105068 United States NS NINDS NIH HHS; S10 OD018040 United States OD NIH HHS |
| فهرسة مساهمة: | Keywords: Brain cancer; Cancer immunotherapy; Immunology; Oncology |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02960230 |
| المشرفين على المادة: | 0 (Cancer Vaccines) 0 (Histones) 0 (Neoplasm Proteins) |
| تواريخ الأحداث: | Date Created: 20200821 Date Completed: 20210216 Latest Revision: 20220729 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7685729 |
| DOI: | 10.1172/JCI140378 |
| PMID: | 32817593 |
| قاعدة البيانات: | MEDLINE |
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