hTERT mRNA dendritic cell vaccination: complete response in a pancreatic cancer patient associated with response against several hTERT epitopes |
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Authors: | Else M Inderberg Suso Svein Dueland Anne-Marie Rasmussen Turid Vetrhus Steinar Aamdal Gunnar Kvalheim Gustav Gaudernack |
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Institution: | (1) Section for Immunology, Oslo University Hospital and University of Oslo, Radiumhospitalet, Montebello, 0310 Oslo, Norway;(2) Department of Clinical Cancer Research, Oslo University Hospital, Radiumhospitalet, Oslo, Norway;(3) Department of Radiology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway;(4) Department of Cellular Therapy, Oslo University Hospital, Radiumhospitalet, Oslo, Norway; |
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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. |
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