"ATIM-32. PHASE IIA CLINICAL TRIAL EVALUATING DENDRITIC CELL VACCINE FOR THE TREATMENT OF LOW-GRADE GLIOMAS Diana Moughon1, Richard Everson1, Sylvia Odesa1, Horacio Soto1, Emma Billingslea-Yoon1, Shaina Sedighim1, Joey Orpilla1, Jeffrey Lin2, Robert Prins1 and Linda Liau1; 1UCLA Neurosurgery, Los Angeles, CA, USA, 2UCLA David Geffen School of Medicine, Los Angeles, CA, USA" We conducted an exploratory phase IIa clinical trial to evaluate the safety and efficacy of autologous tumor lysate-pulsed dendritic cell vaccine therapy in patients with low grade gliomas. Five patients, three with newly-diagnosed and two with recurrent grade II gliomas, enrolled and each received at least one injection of the vaccine. The treatment was welltolerated with only mild side effects such as headache, myalgia and fatigue. There were no grade 3 or 4 adverse events. Interestingly, the patient with the longest progression-free survival, almost 43 months, was 85 years of age at the time of surgery with a diagnosis of IDH1-wildtype 1p/19q-intact astrocytoma, the most aggressive pathology in the trial. The patient whose tumor has not yet progressed, with a TTP >27 months to date, was one of the recurrent tumors at the time of vaccine. Antibody responses to IDH1 R132H mutation, a known neoantigen present in 4/5 tumors, were measured and found to be present in all four patients with IDH mutant tumors by ELISA. We analyzed pre- and post-vaccine tumor specimens of two patients and found significant increases of CD8+ PD-1+ tumor-infiltrating lymphocytes (TILs), but no significant increase of PD-L1 expression in the tumor cells themselves. There was no significant difference in time to progression for the patients in this clinical trial compared control patients who were matched for tumor grade, type, recurrence number, IDH1 status and 1p/19q status. Such findings indicate that further research is warranted to understand why certain low-grade tumors respond better to the vaccine than others. There was also evidence of a PD-1+ cytotoxic T-cell infiltration induced by the vaccine that may benefit from combined PD-1 blockade therapy.
"ATIM-33. PROTEIN MICROARRAY ANALYSIS OF GLIOBLASTOMA PATIENT SERA BEFORE AND AFTER DENDRITIC CELL VACCINATION Alexander Tucker, Richard Everson, Joey Orpilla, Horacio Soto, Frank Yuan, Linda Liau and Robert Prins; UCLA Neurosurgery, Los Angeles, CA, USA" Immunotherapy with dendritic cell (DC) vaccination for the treatment of glioblastoma (GBM), appears to correlate with prolonged survival in some, but not all patients treated. While some patients exhibit increased T-cell infiltration after DC vaccination, antibody responses have been under explored as an alternative hypothesis as to why there is heterogeneity in survival outcomes. To investigate this, we used a microarray with 9,000 full-length human proteins to obtain autoantibody profiles of sera from two patients (Patient A and B) with GBM before and after DC vaccination. Aside from a large difference in patient survival (67 months vs 10 months), the tumors appeared similar by standard molecular pathologic analysis (both tumors have unmethylated MGMT promotors and similar Ki-67 indices, although Patient B’s tumor showed positive expression of EGFRvIII while this was not observed in Patient A). There was an increase in the signal intensity to more protein targets after vaccination in Patient A than B (3,843 vs 709) and only one antibody was significantly elevated in both patients. This antibody is directed against a protein encoded by the BCL2-associated athanogene 5 variant 2 (BAG 5v2), believed to have antiapoptotic functions. Upregulation of BAG 5v2 gene expression has been implicated in other solid malignancies of the body such as prostate, breast, colon, and pancreatic cancers. This findings suggests that BAG 5v2 could be a novel cancer biomarker/therapeutic target, but is being validated by expanding the project to include 11 more patients. Comprehensive analysis of antitumor antibody responses generated by DC vaccination may allow us to predict which patients will benefit from treatment, monitor response or progression and perhaps learn more about the biological mechanism by which DC vaccination works.
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