Cellular-Based Immunotherapies for Patients with Glioblastoma Multiforme
Table 1
Synopsis of DC-based immunotherapy trials for GBM patients.
Patients
Phase
Route
Antigen format
Immune response
Clinical response
References
22 patients (13 recurrent GBM, 5 AA, 3 AO, 1 AOA)
Phase I/II
Intranodal + intramuscular injections of poly-ICLC
Synthetic peptides for GAAs
Induced positive immune responses against at least one of the GAAs in PBMCs in 58% of patients (after 4 vaccinations). Significant upregulation: interferon-alpha and CXCL10.
4 recurrent GBM are progression free for at least 12 months; 1 CR (recurrent GBM). Median TTP: 4 months.
Intradermal + intramuscular injections of poly-ICLC
Autologous tumor lysate + imiquimod or poly-ICLC
No dose-limiting toxicity. Tumor samples with a mesenchymal gene expression signature had a higher number of CD3+ and CD8+ tumor-infiltrating lymphocytes
Newly diagnosed: median OS: 35.9 months, with a mean follow-up time of more than 4 years, and 1-, 2-, and 3-year survival rates of 93%, 77%, and 58%, respectively. Recurrent: median OS was 17.9 months from the time of initial glioblastoma diagnosis. OS was significantly longer for those who received DC vaccination at initial diagnosis compared with those who enrolled in this trial at the time of recurrence.
DTH (9/21 at time of diagnosis, 9/17 after 2 vaccinations)
3-month PFS; OS: 9.6 months; 24-month OS: 14.8%; total resection is a predictor for better PFS; younger age and total resection are predictors for better OS.
Postvaccine antigen-directed IFNg response in PBMCs (17/34); DTH-test resulted in cutaneous GBM in 1 patient (DTH was subsequently discontinued)
Newly diagnosed: 8/17 (47%) vaccine responders versus. 3/15 (20%) nonresponders; Recurrent: TTS, and d; TTP, and d (8 responders and 13 nonresponders); TTP, and d (8 responders and 15 nonresponders)
24 patients (18 recurrent GBM, 6 grade III glioma)
Phase I/II
Intradermal or intradermal + intratumoral (Ommaya reservoir)
Autologous tumor-lysate
DTH to tumor lysate (8/24); ATR PBMC (7/24) (IFN-gamma ELISPOT)
1 PR, 3 MR, 6 SD (GBM); 4 SD (Grade III glioma); median OS: 16 months versus 13.3 months; longer survival if DC maturation or IC injection. One grade IV neurotoxicity event (stupor) observed.