A randomized pilot phase I study of modified carcinoembryonic antigen (CEA) peptide (CAP1-6D)/montanide/GM-CSF-vaccine in patients with pancreatic adenocarcinoma

Journal for ImmunoTherapy of Cancer

Hedy L Kindler¹  Thomas F Gajewski⁴  Theodore Karrison²  Azadeh Namakydoust³  Cara Rosenbaum⁴  Blase N Polite⁴  Daniel VT Catenacci⁴  Mebea Aklilu³  Rangesh Kunnavakkam²  Yuanyuan Zha⁴  Daniel M Geynisman⁴ 

[1] Section of Hematology/Oncology, Department of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637, USA;Department of Health Studies, University of Chicago, Chicago, IL, USA;Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA;University of Chicago Cancer Research Center, Chicago, IL, USA

关键词: CEA;    Immunization;    Vaccine;    Pancreatic Cancer;   

Others  :  815041
DOI  :  10.1186/2051-1426-1-8

 received in 2013-02-26, accepted in 2013-04-15,  发布年份 2013

【 摘 要 】

Background

CEA is expressed in >90% of pancreatic cancers (PC) and may be an appropriate immunotherapy target. CEA is poorly immunogenic due to immune tolerance; CAP1-6D, an altered peptide ligand can help bypass tolerance. We conducted a pilot randomized phase I trial in PC patients to determine the peptide dose required to induce an optimal CD8⁺ T cell response.

Methods

Patients with a PS 0-1, HLA-A2+ and CEA-expressing, previously-treated PC were randomized to receive 10 μg (arm A), 100 μg (arm B) or 1000 μg (arm C) of CEA peptide emulsified in Montanide and GM-CSF, given every 2 weeks until disease progression.

Results

Sixty-six patients were screened and 19 enrolled of whom 14 received at least 3 doses of the vaccine and thus evaluated for the primary immunologic endpoint. A median of 4 cycles (range 1-81) was delivered. Median and mean peak IFN-γ T cell response by ELISPOT (spots per 10⁴ CD8⁺ cells, Arm A/B/C) was 11/52/271 (A vs. C, p = 0.028) for medians and 37/148/248 (A vs. C, p = 0.032) for means. T cell responses developed or increased in 20%/60%/100% of pts in Arms A/B/C. Seven of the 19 patients remain alive at a minimum 32 months from trial initiation, including three with unresectable disease.

Conclusions

The T cell response in this randomized phase I trial was dose-dependent with the 1 mg CEA peptide dose eliciting the most robust T cell responses. A signal of clinical benefit was observed and no significant toxicity was noted. Further evaluation of 1 mg CEA peptide with stronger adjuvants, and/or combined with agents to overcome immune inhibitory pathways, may be warranted in PC pts.

Trial registration

ClinicalTrials.gov NCT00203892

【 授权许可】

   
2013 Geynisman et al.; licensee BioMed Central Ltd.

【 图 表 】

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