Introduction: We have previously reported the safety and feasibility of vaccinating recurrent malignant glioma patients with irradiated autologous cells mixed with irradiated GM-K562 cells. Here, we report the impact of vaccination on the expression of T-lymphocyte co-stimulatory and co-inbhibitory molecules as well as on regulatory T-lymphocytes. Furthermore, we explored the impact of vaccination on patient humoral immune responses with particular attention to antibody titers against molecules associated with tumor angiogenesis.
Methods: Blood was collected from 9 of 10 treated patients at regular intervals and submitted for immune analysis. 5-color flow cytometry was employed after staining of whole blood by an immunophenotyping antibody panel. Antibody titers to tumor-associated antigens were measured by ELISA of patient plasma – all assays were performed in duplicate. Treatment-associated change in percent expression of various markers was analyzed via the non-parametric sign-rank test. P< 0.05 was considered statistically significant.
Results: In patients undergoing craniotomy for recurrent malignant glioma, vaccination with irradiated autologous tumor cells and irradiated GM-K562 cells was associated with statistically significant increases in CD4+ T-lymphocyte expression of costimulatory molecules OX40 and 4-1BB (CD137). CD8+ T-lymphocytes saw increased expression of 4-1BB as well. Likewise, there were increases in CD4+ T-lymphocyte expression of CTLA-4, PD1, and FOXP3 – each of which is associated with negative immune regulation and are targetable with existing monoclonal antibodies. 7 of 9 patients had marked treatment-driven increases in antibody titers to Angiopoietin 2, which may represent a novel glioma vasculature-associated antigen.
Conclusions: Vaccination with irradiated autologous tumor cells mixed with irradiated GM-K562 cells in patients with recurrent malignant glioma is biologically active and activates both T-lymphoctes and humoral antitumor immunity. Vaccine-induced expression of costimulatory molecules may provide the rationale for combination therapies with either co-stimulatory receptor agonist or co-inhibitory receptor antagonist molecules.
Patient Care: We are investigating a novel vaccination strategy, which is safe and biologically active and may allow survival benefit in patients with recurrent glioma
Learning Objectives: Participants will understand the potential role of immunotherapy in patients with malignant glioma; participants will understand the importance of immune monitoring for patients undergoing vaccination for cancer.