Abstract
<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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<sup>6</sup> GM-K562 cells or 1 × 10<sup>7</sup> GM-K562 cells. Eligibility required <i>a priori</i> 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.</p><p><b>Results:</b> 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<sup>+</sup> cells and PD-1 and 4-1BB by CD8<sup>+</sup> cells. Activation was coupled with vaccine-associated increase in the frequency of regulatory CD4<sup>+</sup> T lymphocytes.</p><p><b>Conclusions:</b> Vaccination with irradiated autologous tumor cells mixed with GM-K562 cells is feasible, well tolerated, and active in patients with recurrent malignant glioma. <i>Clin Cancer Res; 22(12); 2885–96. ©2016 AACR</i>.</p></div>
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