| Modified vaccinia virus Ankara delivers a robust surrogate marker for immune monitoring to sarcoma cells even if cells are being exposed to chemotherapy and heat treatment. | |
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MedLine Citation:
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PMID: 22235783 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Purpose: Adding hyperthermia to chemotherapy improved the clinical outcome of patients with high risk soft tissue sarcoma. Further improvement might be possible if combined with vaccination strategies. As no sarcoma-associated antigens are known, the ectopic expression of a surrogate marker for which immune monitoring tools are available, is envisaged. We tested surrogate marker transfer into sarcoma cells in vitro using modified vaccinia virus Ankara (MVA), which has well established clinical safety. We examined its robustness against standard sarcoma treatment modalities, such as ifosfamide and hyperthermia. Materials and methods: We transduced sarcoma cell lines and primary tumour cells from sarcoma patients with MVA encoding the human tyrosinase gene (MVA-hTyr). Kinetics of tyrosinase expression and the potency to activate tyrosinase-specific cytotoxic T cells were assessed. In addition cells were exposed to chemotherapy and heat, imitating the clinical setting. Results: Tyrosinase was ectopically expressed in sarcoma cells. Infected cells presented tyrosinase epitopes for T cell recognition even if exposed to ifosfamide/heat. Conclusions: As sarcoma patients receive surgery up front or after neoadjuvant systemic chemotherapy/hyperthermia, tumour material is generally available. Our data document that primary sarcoma cells can be infected with MVA-hTyr in vitro and antigen presentation is not affected by ifosfamide or heat treatment. Infected cells can serve as a source for vaccine preparation. MVA-hTyr infection of tumour cells lacking defined antigens is a feasible system to introduce a robust surrogate marker to provide an immune monitoring marker for assessing the induction of antigen-specific T cell activation. |
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Authors:
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Katharina Tschoep-Lechner; Ingo Drexler; Doreen Hammer; Daniel Neumann; Heike Pohla; Gerd Sutter; Elfriede Noessner; Rolf-Dieter Issels |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group Volume: 28 ISSN: 1464-5157 ISO Abbreviation: Int J Hyperthermia Publication Date: 2012 |
Date Detail:
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Created Date: 2012-01-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8508395 Medline TA: Int J Hyperthermia Country: England |
Other Details:
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Languages: eng Pagination: 33-42 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine III, Klinikum Grosshadern Medical Centre, Ludwig Maximilians University , Munich , Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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