Vaccination with dendritic cells loaded with allogeneic brain tumor cells for recurrent malignant brain tumors induces a CD4(+)IL17(+) response.

Autor: Olin MR; Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA., Low W; Department of Neurosurgery, University of Minnesota, 2001 6th St SE, Rm 4-216, Minneapolis, MN 55455, USA., McKenna DH; Department of Laboratory Medicine and Pathology, University of Minnesota, 8609B, 420 Delaware St SE, Minneapolis, MN 55455, USA., Haines SJ; Department of Radiology, University of Minnesota, 8292A, 420 Delaware St SE, Minneapolis, MN 55455, USA., Dahlheimer T; Department of Laboratory Medicine and Pathology, 200 First St, Mayo Clinic, Rochester, MN 55901, USA., Nascene D; Department of Radiology, University of Minnesota, 8292A, 420 Delaware St SE, Minneapolis, MN 55455, USA., Gustafson MP; Department of Laboratory Medicine and Pathology, 200 First St, Mayo Clinic, Rochester, MN 55901, USA., Dietz AB; Department of Laboratory Medicine and Pathology, 200 First St, Mayo Clinic, Rochester, MN 55901, USA., Clark HB; Department of Laboratory Medicine and Pathology, University of Minnesota, 8609B, 420 Delaware St SE, Minneapolis, MN 55455, USA., Chen W; Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA., Blazar B; Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA., Ohlfest JR; Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA., Moertel C; Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA.
Jazyk: angličtina
Zdroj: Journal for immunotherapy of cancer [J Immunother Cancer] 2014 Feb 18; Vol. 2, pp. 4. Date of Electronic Publication: 2014 Feb 18 (Print Publication: 2014).
DOI: 10.1186/2051-1426-2-4
Abstrakt: Background: We tested the hypothesis that a novel vaccine developed from autologous dendritic cells (DC) loaded with cells from a unique allogeneic brain tumor cell line (GBM6-AD) would be well-tolerated and would generate an immune response.
Method: Patients with recurrent primary brain tumors underwent vaccination with GBM6-AD/DC vaccine. Subjects were treated at escalating DC cell doses: 5 × 10(6) (one patient), 10 × 10(6) (one patient) and 15 × 10(6) (6 patients). Subcutaneous injections were planned for days 0, 14, 28, 42, 56, and monthly thereafter. The primary endpoint was the safety of the GBM6-AD/DC vaccination. The secondary endpoints were immune response, measured by flow cytometry, and the clinical outcome of tumor response defined by time to progression and overall survival.
Results: Eight patients were treated. The first three patients were treated in the dose escalation phase of the trial; the remaining five patients received the maximum dose of 15 × 10(6) DC. No dose limiting toxicity was observed. The best response per modified McDonald criteria was partial response in one patient. Flow cytometric immune profiling revealed significant differences in CD4(+)IL17(+) lymphocytes and myeloid derived suppressor cell populations between patients characterized as having stable vs. non-stable disease.
Conclusion: This first-in-human study shows that the GBM6-AD/DC vaccine was well tolerated and was associated with an immune response in a subset of patients. No MTD was achieved in this trial. This small-scale pilot provides information for larger scale investigations into the use of this allogeneic vaccine source.
Databáze: MEDLINE
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