hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes
Open Access
- 2 March 2011
- journal article
- case report
- Published by Springer Science and Business Media LLC in Cancer Immunology, Immunotherapy
- Vol. 60 (6), 809-818
- https://doi.org/10.1007/s00262-011-0991-9
Abstract
Immunotherapy targeting the hTERT subunit of telomerase has been shown to induce robust immune responses in cancer patients after vaccination with single hTERT peptides. Vaccination with dendritic cells (DCs) transfected with hTERT mRNA has the potential to induce strong immune responses to multiple hTERT epitopes and is therefore an attractive approach to more potent immunotherapy. Blood samples from such patients provide an opportunity for identification of new, in vivo processed T-cell epitopes that may be clinically relevant. A 62-year-old female patient underwent radical surgery for a pancreatic adenocarcinoma. After relapse, she obtained stable disease on gemcitabine treatment. Due to severe neutropenia, the chemotherapy was terminated. The patient has subsequently been treated with autologous DCs loaded with hTERT mRNA for 3 years. Immunomonitoring was performed at regular intervals following start of vaccination and clinical outcome measured by CT and PET/CT evaluation. The patient developed an immune response against several hTERT-derived Th and CTL epitopes. She presently shows no evidence of active disease based on PET/CT scans. No serious adverse events were experienced and the patient continues to receive regular booster injections. We here provide evidence for the induction of hTERT-specific immune responses following vaccination of a pancreas cancer patient with DCs loaded with hTERT mRNA. These responses are associated with complete remission. A thorough analysis of this patient immune response has provided a unique opportunity to identify novel epitopes, associated with clinical effects. These will be included in future hTERT vaccines.This publication has 28 references indexed in Scilit:
- Naive tumor-specific CD4+ T cells differentiated in vivo eradicate established melanomaThe Journal of Experimental Medicine, 2010
- Consensus Report of the National Cancer Institute Clinical Trials Planning Meeting on Pancreas Cancer TreatmentJournal of Clinical Oncology, 2009
- CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell helpNature, 2009
- Pancreatic cancer stem cells: Fact or fiction?Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2009
- Biological Approaches to Therapy of Pancreatic CancerPancreatology, 2008
- Treatment of Metastatic Melanoma with Autologous CD4+ T Cells against NY-ESO-1New England Journal of Medicine, 2008
- Induction of Tumor-Specific CD4+ and CD8+ T-Cell Immunity in Cervical Cancer Patients by a Human Papillomavirus Type 16 E6 and E7 Long Peptides VaccineClinical Cancer Research, 2008
- Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania majorNature Medicine, 2007
- Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II studyBritish Journal of Cancer, 2006
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000