A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas
Abstract 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...
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Published in | Neuro-oncology (Charlottesville, Va.) Vol. 26; no. 2; pp. 335 - 347 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
US
Oxford University Press
02.02.2024
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract
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. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Undefined-1 ObjectType-Feature-3 content type line 23 Atsuro Saijo, Hirokazu Ogino and Nicholas A Butowski contributed equally to this work. |
ISSN: | 1522-8517 1523-5866 1523-5866 |
DOI: | 10.1093/neuonc/noad185 |