A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma: A phase II trial of safety, efficacy, and immune activation

Lutz Eric, Charles J. Yeo, Keith D. Lillemoe, Barbara Biedrzycki, Barry Kobrin, Joseph Herman, Elizabeth Sugar, Steven Piantadosi, John L. Cameron, Sara Solt, Beth Onners, Irena Tartakovsky, Miri Choi, Rajni Sharma, Peter B. Illei, Hruban Ralph H., Ross A. Abrams, Dung Le, Jaffee Elizabeth, Dan Laheru

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Surgical resection provides the only possibility of cure for pancreas cancer. A standard adjuvant approach has not been established. We tested the safety and efficacy of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-based immunotherapy administered in patients with resected pancreatic adenocarcinoma. Patients andMethods: A single institution phase II study of 60 patients with resected pancreatic adenocarcinoma was performed. Each immunotherapy treatment consisted of a total of 5 × 108 GM-CSF-secreting cells distributed equally among 3 lymph node regions. The first immunotherapy treatment was administered 8 to 10 weeks after surgical resection. Subsequently, patients received 5-FU based chemoradiation. Patientswho remained disease-free after completion of chemoradiotherapy received treatments 2 to 4, each 1 month apart. A fifth and final booster was administered 6 months after the fourth immunotherapy.The primary endpointwas disease free survival and secondary endpoints were overall survival and toxicity, and the induction of mesothelinspecific T cell responses. Results: Themedian disease-free survival is 17.3months (95% CI, 14.6-22.8) with median survival of 24.8 months (95% CI, 21.2-31.6). The administration of immunotherapy was well tolerated. In addition, the postimmunotherapy induction of mesothelin-specific CD8+ T cells in HLA-A1+ and HLA-A2+ patients correlates with disease-free survival. Conclusions: An immunotherapy approach integrated with chemoradiation is safe and demonstrates an overall survival that compares favorably with published data for resected pancreas cancer. These data suggest additional boost immunotherapies given at regular intervals beyond 1 year postsurgery should be tested in future studies, and provide the rationale for conducting a multicenter phase II study.

Original languageEnglish (US)
Pages (from-to)328-335
Number of pages8
JournalAnnals of surgery
Volume253
Issue number2
DOIs
StatePublished - Feb 2011

ASJC Scopus subject areas

  • Surgery

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