Article
作者: Perry, Arie ; Rabbitt, Jane E ; Chang, Susan M ; Shai, Anny ; Phillips, Joanna J ; Butowski, Nicholas A ; Ogino, Hirokazu ; Tedesco, Meghan R ; Gibson, David ; Keler, Tibor ; Saijo, Atsuro ; Hervey-Jumper, Shawn L ; Taylor, Jennie W ; Berger, Mitchel S ; Watchmaker, Payal B ; Molinaro, Annette M ; Shahin, Maryam ; Wang, Albert S ; Okada, Kaori ; Okada, Hideho ; Daras, Mariza ; Mayer-Mokler, Andrea ; Oberheim Bush, Nancy Ann ; Salazar, Andres M ; Hilf, Norbert ; Clarke, Jennifer L
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.