Dendritic Cell Immunotherapy Promising in HLA-A2-Positive Glioblastoma

Patients with HLA-A2–positive glioblastoma multiforme experienced more frequent immune responses to the dendritic-cell immunotherapy IDT-107 than other patients, and immune response appears to be associated with improved survival in these patients, according to results from a phase II study presented the 20th Annual Scientific Meeting of the Society for Neuro-Oncology, held November 19-22 in San Antonio, Texas.  

“HLA-A2–positive immune responders had longer progression-free survival (PFS) than nonresponders,” reported coauthor John S. Yu, MD, founder of ImmunoCellular Therapeutics. The median PFS for responders was 11.2 months vs 7.7 months among nonresponders (P = .032), he said. “The clear association between immune response and survival is an important finding that we believe validates the immunotherapeutic mechanism of ICT-107.”

A total of 124 patients were enrolled in the study and randomized 2:1 to receive either ICT-107 or unincubated dendritic cells. ICT-107 consists of autologous dendritic cells incubated with six synthetic peptide CTL epitopes that target glioblastoma tumor– and stem cell–associated antigens.

Using ELISPOT immunologic assay, which measures the number of peripheral antigen-specific CTLs that secrete IFN-gamma, the researchers used a “novel analytical method factoring in four metrics of response including magnitude of response and statistical significance” to identify responders. Sixty percent of HLA-A2–positive patients receiving ICT-107 experienced a significantly increased immune response, compared with 36% of patients in the control group, reported Yu.

Among HLA-A2–positive patients, IL-12 secretion by dendritic cells was associated with immune response, Dr. Yu reported.

“There was no impact of MGMT status on outcomes,” he noted.

An unexpected increase was reported for immune response in some control patients after treatment with unincubated dendritic cells, possibly suggesting that activated dendritic cells without peptide loading is immunologically active, Dr. Yu noted. The phase III trial uses autologous monocytes instead of activated dendritic cells, as a control-arm treatment.