Skip to main content
Download PDF
- Main
A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas
- Saijo, Atsuro;
- Ogino, Hirokazu;
- Butowski, Nicholas A;
- Tedesco, Meghan R;
- Gibson, David;
- Watchmaker, Payal B;
- Okada, Kaori;
- Wang, Albert S;
- Shai, Anny;
- Salazar, Andres M;
- Molinaro, Annette M;
- Rabbitt, Jane E;
- Shahin, Maryam;
- Perry, Arie;
- Clarke, Jennifer L;
- Taylor, Jennie W;
- Daras, Mariza;
- Bush, Nancy Ann Oberheim;
- Hervey-Jumper, Shawn L;
- Phillips, Joanna J;
- Chang, Susan M;
- Hilf, Norbert;
- Mayer-Mokler, Andrea;
- Keler, Tibor;
- Berger, Mitchel S;
- Okada, Hideho
Published Web Location
https://doi.org/10.1093/neuonc/noad185Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
Main Content
For improved accessibility of PDF content, download the file to your device.
Enter the password to open this PDF file:
File name:
-
File size:
-
Title:
-
Author:
-
Subject:
-
Keywords:
-
Creation Date:
-
Modification Date:
-
Creator:
-
PDF Producer:
-
PDF Version:
-
Page Count:
-
Page Size:
-
Fast Web View:
-
Preparing document for printing…
0%