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

Michael R. Olin, Walter Low, David H. McKenna, Stephen J. Haines, Tambra Dahlheimer, David Nascene, Michael Gustafson, Allan B Dietz, H. B. Clark, Wei Chen, Bruce Blazar, John R. Ohlfest, Christopher Moertel

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 × 106 (one patient), 10 × 106 (one patient) and 15 × 106 (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 × 106 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.

Original languageEnglish (US)
Article number4
JournalJournal for ImmunoTherapy of Cancer
Volume2
Issue number1
DOIs
StatePublished - Feb 18 2014

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Brain Neoplasms
Dendritic Cells
Vaccination
Vaccines
Subcutaneous Injections
Tumor Cell Line
Flow Cytometry
Lymphocytes
Safety
Survival

Keywords

  • Brain tumor
  • Dendritic cell
  • Immunotherapy
  • Vaccine

ASJC Scopus subject areas

  • Oncology
  • Immunology and Allergy
  • Cancer Research
  • Molecular Medicine
  • Pharmacology
  • Immunology

Cite this

Vaccination with dendritic cells loaded with allogeneic brain tumor cells for recurrent malignant brain tumors induces a CD4+IL17+ response. / Olin, Michael R.; Low, Walter; McKenna, David H.; Haines, Stephen J.; Dahlheimer, Tambra; Nascene, David; Gustafson, Michael; Dietz, Allan B; Clark, H. B.; Chen, Wei; Blazar, Bruce; Ohlfest, John R.; Moertel, Christopher.

In: Journal for ImmunoTherapy of Cancer, Vol. 2, No. 1, 4, 18.02.2014.

Research output: Contribution to journalArticle

Olin, Michael R. ; Low, Walter ; McKenna, David H. ; Haines, Stephen J. ; Dahlheimer, Tambra ; Nascene, David ; Gustafson, Michael ; Dietz, Allan B ; Clark, H. B. ; Chen, Wei ; Blazar, Bruce ; Ohlfest, John R. ; Moertel, Christopher. / Vaccination with dendritic cells loaded with allogeneic brain tumor cells for recurrent malignant brain tumors induces a CD4+IL17+ response. In: Journal for ImmunoTherapy of Cancer. 2014 ; Vol. 2, No. 1.
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AU - Low, Walter

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AU - Haines, Stephen J.

AU - Dahlheimer, Tambra

AU - Nascene, David

AU - Gustafson, Michael

AU - Dietz, Allan B

AU - Clark, H. B.

AU - Chen, Wei

AU - Blazar, Bruce

AU - Ohlfest, John R.

AU - Moertel, Christopher

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AB - 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 × 106 (one patient), 10 × 106 (one patient) and 15 × 106 (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 × 106 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.

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