Phase I trial of adjuvant mature autologous dendritic cell/allogeneic tumor lysate vaccines in combination with temozolomide in newly diagnosed glioblastoma.

Autor:	Parney IF; Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota, USA., Anderson SK; Department of Quantitative Health Sciences, Mayo Clinic Cancer Center, Rochester, Minnesota, USA., Gustafson MP; Nyberg Human Cell Therapy Lab, Division of Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, Arizona, USA., Steinmetz S; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA., Peterson TE; Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota, USA., Kroneman TN; Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Raghunathan A; Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., O'Neill BP; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA., Buckner JC; Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA., Solseth M; Immune Progenitor and Cellular Therapy (IMPACT) Laboratory, Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA., Dietz AB; Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2022 Jun 24; Vol. 4 (1), pp. vdac089. Date of Electronic Publication: 2022 Jun 24 (Print Publication: 2022).
DOI:	10.1093/noajnl/vdac089
Abstrakt:	Background: Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs. Here, we report a phase I study using this optimized DC vaccine in combination with standard therapy. Methods: Following surgical resection and radiation with concurrent temozolomide (TMZ), newly diagnosed adult GBM patients received intradermal DC vaccines plus TMZ. Primary endpoints were safety and feasibility. Immune and treatment responses were recorded. Results: Twenty-one patients were enrolled in this study. One progressed between leukapheresis and vaccine manufacture. Twenty patients received treatment per protocol. Vaccine doses (≥15) were generated following a single leukapheresis for each patient. No dose-limiting vaccine toxicities were encountered. One patient had symptomatic, histologically proven pseudoprogression. Median progression-free survival was 9.7 months. Median overall survival was 19 months. Overall survival was 25% at 2 years and 10% at 4 years. One patient remains progression-free 5 years after enrollment. Specific CD8 T-cell responses for the tumor-associated antigen gp100 were seen post-vaccination. Patients entered the trial with a leukocyte deficit compared to healthy donors which partly normalized over the course of therapy. Conclusions: This vaccine platform is safe and highly feasible in combination with standard therapy for newly diagnosed patients. Imaging, histological, survival, and immunological data suggest a positive biological response to therapy that warrants further investigation. (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Databáze:	MEDLINE
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