Treatment > Immunotherapy

Abstract

Vaccination with Tumor Lysate-Pulsed Dendritic Cells Elicits Antigen-Specific, Cytotoxic T-Cells in Patients with Malignant Glioma

¹Maxine Dunitz Neurosurgical Institute and ²Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California

Fourteen patients were thrice vaccinated 2 weeks apart with autologous DCs pulsed with tumor lysate. 
Peripheral blood mononuclear cells were differentiated into phenotypically and functionally confirmed DCs. 
Vaccination with tumor lysate-pulsed DCs was safe, and no evidence of autoimmune disease was noted. 
Ten patients were tested for the development of cytotoxicity through a quantitative PCR-based assay. 
Six of 10 patients demonstrated robust systemic cytotoxicity as demonstrated by IFN-γ expression by peripheral blood mononuclear cells in response to tumor lysate after vaccination.  
Using HLA-restricted tetramer staining, we identified a significant expansion in CD8+ antigen-specific T-cell clones against one or more of tumor-associated antigens MAGE-1, gp100, and HER-2 after DC vaccination in four of nine patients. 
A significant CD8+ T-cell infiltrate was noted intratumorally in three of six patients who underwent reoperation. 
The median survival for patients with recurrent glioblastoma multiforme in this study (n = 8) was 133 weeks. 

This Phase I study demonstrated the feasibility, safety, and bioactivity of an autologous tumor lysate-pulsed DC vaccine for patients with malignant glioma. We demonstrate for the first time the ability of an active immunotherapy strategy to generate antigen-specific cytotoxicity in brain tumor patients.