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


METHODS
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.


CONCLUSIONS
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.
Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA.
Michael R
MR
Olin
Department of Neurosurgery, University of Minnesota, 2001 6th St SE, Rm 4-216, Minneapolis, MN 55455, USA.
Walter
W
Low
Department of Laboratory Medicine and Pathology, University of Minnesota, 8609B, 420 Delaware St SE, Minneapolis, MN 55455, USA.
David H
DH
McKenna
Department of Radiology, University of Minnesota, 8292A, 420 Delaware St SE, Minneapolis, MN 55455, USA.
Stephen J
SJ
Haines
Department of Laboratory Medicine and Pathology, 200 First St, Mayo Clinic, Rochester, MN 55901, USA.
Tambra
T
Dahlheimer
Department of Radiology, University of Minnesota, 8292A, 420 Delaware St SE, Minneapolis, MN 55455, USA.
David
D
Nascene
Department of Laboratory Medicine and Pathology, 200 First St, Mayo Clinic, Rochester, MN 55901, USA.
Michael P
MP
Gustafson
Department of Laboratory Medicine and Pathology, 200 First St, Mayo Clinic, Rochester, MN 55901, USA.
Allan B
AB
Dietz
Department of Laboratory Medicine and Pathology, University of Minnesota, 8609B, 420 Delaware St SE, Minneapolis, MN 55455, USA.
H Brent
HB
Clark
Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA.
Wei
W
Chen
Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA.
Bruce
B
Blazar
Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA.
John R
JR
Ohlfest
Department of Pediatrics and the Masonic Cancer Center, University of Minnesota, 3-136 CCRB, 2231 6th St SE, Minneapolis, MN 55455, USA.
Christopher
C
Moertel
Brain tumor; Dendritic cell; Immunotherapy; Vaccine