دورية أكاديمية
Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma.
| العنوان: | Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma. |
|---|---|
| المؤلفون: | Johanns TM; Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri.; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, Missouri.; The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri., Garfinkle EAR; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio., Miller KE; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio., Livingstone AJ; Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri., Roberts KF; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri., Rao Venkata LP; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio., Dowling JL; The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.; Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri., Chicoine MR; Department of Neurosurgery, University of Missouri in Columbia, Columbia, Missouri., Dacey RG; Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri., Zipfel GJ; The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.; Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri., Kim AH; The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.; Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri., Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio.; Department of Pediatrics, Ohio State University College of Medicine, Columbus, Ohio., Dunn GP; Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts.; Brain Tumor Immunology and Immunotherapy Program, Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jul 01; Vol. 30 (13), pp. 2729-2742. |
| نوع المنشور: | Journal Article |
| 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: | Glioblastoma*/immunology , Glioblastoma*/therapy , Glioblastoma*/genetics , Glioblastoma*/pathology , Cancer Vaccines*/immunology , Cancer Vaccines*/administration & dosage , Cancer Vaccines*/therapeutic use , Vaccines, Subunit*/immunology , Vaccines, Subunit*/administration & dosage , Vaccines, Subunit*/therapeutic use , Precision Medicine*/methods , Antigens, Neoplasm*/immunology, Humans ; Female ; Male ; Middle Aged ; Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Adult ; Aged ; Immunotherapy/methods ; Protein Subunit Vaccines |
| مستخلص: | Purpose: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax. Patients and Methods: In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209). Results: Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFNγ-ELISPOT assay. A statistically significant increase in IFNγ producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells. Conclusions: Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM. (©2024 The Authors; Published by the American Association for Cancer Research.) |
| References: | Oncoimmunology. 2019 Jan 25;8(4):e1561106. (PMID: 30906654) Cancer Discov. 2022 Jan;12(1):154-171. (PMID: 34610950) World J Clin Oncol. 2023 Apr 24;14(4):138-159. (PMID: 37124134) Neuro Oncol. 2022 Nov 2;24(11):1935-1949. (PMID: 35511454) Genome Med. 2019 Aug 28;11(1):56. (PMID: 31462330) Genome Biol. 2015 Jan 20;16:6. (PMID: 25600152) Nature. 2019 Jan;565(7738):240-245. (PMID: 30568303) J Virol. 2015 Apr;89(8):4517-26. (PMID: 25653453) Nat Genet. 2023 Oct;55(10):1686-1695. (PMID: 37709863) Genome Med. 2016 Jan 29;8(1):11. (PMID: 26825632) Neuro Oncol. 2023 Feb 14;25(2):339-350. (PMID: 35849035) Cell. 2020 Oct 15;183(2):347-362.e24. (PMID: 33064988) Neuro Oncol. 2018 Mar 27;20(4):472-483. (PMID: 29244145) PLoS Comput Biol. 2014 Aug 07;10(8):e1003665. (PMID: 25102416) Nature. 2019 Jan;565(7738):234-239. (PMID: 30568305) Nature. 2017 Jul 13;547(7662):217-221. (PMID: 28678778) PLoS One. 2019 Mar 14;14(3):e0213684. (PMID: 30870493) N Engl J Med. 2005 Mar 10;352(10):997-1003. (PMID: 15758010) Neuro Oncol. 2023 Jan 5;25(1):123-134. (PMID: 35419607) Nat Med. 2019 Mar;25(3):477-486. (PMID: 30742122) Pharmaceutics. 2022 May 10;14(5):. (PMID: 35631612) Cancer Cell. 2022 Sep 12;40(9):1010-1026.e11. (PMID: 36027916) Nature. 2023 Jun;618(7963):144-150. (PMID: 37165196) Front Immunol. 2021 Mar 11;12:640725. (PMID: 33777034) N Engl J Med. 2005 Mar 10;352(10):987-96. (PMID: 15758009) Neuro Oncol. 2021 Oct 5;23(12 Suppl 2):iii1-iii105. (PMID: 34608945) |
| معلومات مُعتمدة: | The Knight and Christopher Davidson Family Fund; K12 CA167540 United States CA NCI NIH HHS; R01NS112712 National Institute of Neurological Disorders and Stroke (NINDS); The Schnuck Family Fund; The Alvin J. Siteman Cancer Center Investment Program; R01 NS112712 United States NS NINDS NIH HHS; The Foundation for Barnes-Jewish Hospital; K12CA167540 National Institutes of Health (NIH); Nationwide Foundation Innovation Fund |
| المشرفين على المادة: | 0 (Cancer Vaccines) 0 (Vaccines, Subunit) 0 (Antigens, Neoplasm) 0 (Protein Subunit Vaccines) |
| تواريخ الأحداث: | Date Created: 20240419 Date Completed: 20240701 Latest Revision: 20240703 |
| رمز التحديث: | 20240703 |
| مُعرف محوري في PubMed: | PMC11215407 |
| DOI: | 10.1158/1078-0432.CCR-23-3077 |
| PMID: | 38639919 |
| قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!