A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas.

التفاصيل البيبلوغرافية
العنوان:	A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas.
المؤلفون:	Saijo A; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Internal Medicine, Tokushima Prefecture Naruto Hospital, Tokushima, Japan., Ogino H; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Respiratory Medicine & Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan., Butowski NA; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Tedesco MR; Department of Neurology, University of California, San Francisco, CA, USA., Gibson D; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Watchmaker PB; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Okada K; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Wang AS; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, CA, USA., Shai A; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, CA, USA., Salazar AM; Oncovir Inc., Washington, DC, USA., Molinaro AM; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.; Immatics Biotechnologies GmbH, Tuebingen, Germany., Rabbitt JE; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Shahin M; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Perry A; Department of Pathology, University of California, San Francisco, CA, USA., Clarke JL; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Neurology, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Taylor JW; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Neurology, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Daras M; Department of Neurological Surgery, University of California, San Francisco, CA, USA., Oberheim Bush NA; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Department of Neurology, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Hervey-Jumper SL; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Phillips JJ; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.; Department of Pathology, University of California, San Francisco, CA, USA., Chang SM; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Hilf N; Immatics Biotechnologies GmbH, Tuebingen, Germany., Mayer-Mokler A; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Keler T; Celldex Theraepeutics, Inc., Hampton, NJ, USA., Berger MS; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA., Okada H; Department of Neurological Surgery, University of California, San Francisco, CA, USA.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
المصدر:	Neuro-oncology [Neuro Oncol] 2024 Feb 02; Vol. 26 (2), pp. 335-347.
نوع المنشور:	Randomized Controlled Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2010- : Oxford : Oxford University Press Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
مواضيع طبية MeSH:	Glioma/drug therapy , Cancer Vaccines , Peptides* , Antibodies, Monoclonal, Humanized*, Humans ; Pilot Projects ; Leukocytes, Mononuclear ; Prospective Studies ; Cell Differentiation ; Tumor Microenvironment
مستخلص:	Background: Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients. Methods: We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950 + poly-ICLC and varlilumab (Arm 1) or IMA950 + poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines. Results: A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment. Conclusion: The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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معلومات مُعتمدة:	P50 CA097257 United States CA NCI NIH HHS; R21 CA233856 United States CA NCI NIH HHS; R35 NS105068 United States NS NINDS NIH HHS; 1R35NS105068 United States NH NIH HHS
فهرسة مساهمة:	Keywords: IMA950; immunotherapy; low-grade glioma; poly-ICLC; varlilumab
المشرفين على المادة:	0 (IMA950) 0125DUV5XC (varlilumab) 0 (Cancer Vaccines) 0 (Peptides) 0 (Antibodies, Monoclonal, Humanized)
تواريخ الأحداث:	Date Created: 20230927 Date Completed: 20240205 Latest Revision: 20240521
رمز التحديث:	20240521
مُعرف محوري في PubMed:	PMC10836773
DOI:	10.1093/neuonc/noad185
PMID:	37758193
قاعدة البيانات:	MEDLINE

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تدمد:	1523-5866
DOI:	10.1093/neuonc/noad185