방사선의학 웹진

바로가기  >

Abstract

PURPOSE:

Recurrent malignant glioma carries a dismal prognosis, and novel therapies are needed. We examined the feasibility and safety of vaccination with irradiated autologous glioma cells mixed with irradiated GM-K562 cells in patients undergoing craniotomy for recurrent malignant glioma.

EXPERIMENTAL DESIGN:

We initiated a phase I study examining the safety of 2 doses of GM-K562 cells mixed with autologous cells. Primary endpoints were feasibility and safety. Feasibility was defined as the ability for 60% of enrolled subjects to initiate vaccination. Dose-limiting toxicity was assessed via a 3+3 dose-escalation format, examining irradiated tumor cells mixed with 5 × 10(6) GM-K562 cells or 1 × 10(7) GM-K562 cells. Eligibility required a priori indication for resection of a recurrent high-grade glioma. We measured biological activity by measuring delayed type hypersensitivity (DTH) responses, humoral immunity against tumor-associated antigens, and T-lymphocyte activation.

RESULTS:

Eleven patients were enrolled. Sufficient numbers of autologous tumor cells were harvested in 10 patients, all of whom went on to receive vaccine. There were no dose-limiting toxicities. Vaccination strengthened DTH responses to irradiated autologous tumor cells in most patients, and vigorous humoral responses to tumor-associated angiogenic cytokines were seen as well. T-lymphocyte activation was seen with significantly increased expression of CTLA-4, PD-1, 4-1BB, and OX40 by CD4(+) cells and PD-1 and 4-1BB by CD8(+) cells. Activation was coupled with vaccine-associated increase in the frequency of regulatory CD4(+) T lymphocytes.

CONCLUSIONS:

Vaccination with irradiated autologous tumor cells mixed with GM-K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. 

Author information

Curry WT Jr1, Gorrepati R2, Piesche M3, Sasada T4, Agarwalla P2, Jones PS2, Gerstner ER5, Golby AJ6, Batchelor TT5, Wen PY7, Mihm MC8, Dranoff G9.​

1Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts. Cancer Center, Massachusetts General Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts. wcurry@mgh.harvard.edu.

2Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.

3Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts. Department of Biomedicine, Aarhus University, Aarhus, Denmark.

4Cancer Vaccine Center, Dana Farber Cancer Institute, Boston, Massachusetts.

5Cancer Center, Massachusetts General Hospital, Boston, Massachusetts. Harvard Medical School, Boston, Massachusetts.

6Harvard Medical School, Boston, Massachusetts. Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.

7Harvard Medical School, Boston, Massachusetts. Division of Neuro-oncology, Dana Farber Cancer Institute, Boston, Massachusetts.

8Harvard Medical School, Boston, Massachusetts. Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.

9Harvard Medical School, Boston, Massachusetts. Department of Medicine, Dana Farber Cancer Institute, Boston, Massachusetts. Cancer Vaccine Center, Dana Farber Cancer Institute, Boston, Massachusetts.