HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Strong immunogenic potential of a B7 retroviral expression vector: generation of HLA-B7-restricted CTL response against selectable marker genes.

Abstract
The stimulation of a specific immune response is an attractive goal in cancer therapy. Gene transfer of co-stimulatory molecules and/or cytokine genes into tumor cells and the injection of these genetically modified cells leads to tumor rejection by syngeneic hosts and the induction of tumor immunity. However, the development of host immune response could be either due to the introduced immunomodulatory genes or due to vector components. In this study, human renal cell carcinoma cell lines were modified by a retrovirus to express the co-stimulatory molecule B7-1 together with the hygromycin/thymidine kinase fusion protein (HygTk) as positive and negative selection markers. These B7-1-transduced renal cell carcinoma cell lines were able significantly to activate allogeneic T cell proliferation. The cytolytic activity of these T cells was determined by employing several transduced and nontransduced renal cell carcinoma cell lines as targets. Evidence for a strong vector-specific T cell reactivity induced by the Hyg/Tk protein was obtained in autologous renal cell carcinoma systems. Antibody blocking experiments as well as peptide binding assays demonstrated an HLA-B7-restricted T cell response directed against both the Hyg and the Tk genes. Thus, the vector itself may mask the generation of immune reactivity against tumor antigens and may even detract from it. Vectors with immunogenic potential may be useful for tumor vaccination via cross priming in vivo, whereas antivector reactivities would be detrimental in situations where gene defects are being corrected and where long term expression of a therapeutic protein is required.
AuthorsD Jung, E Jaeger, S Cayeux, T Blankenstein, C Hilmes, J Karbach, U Moebius, A Knuth, C Huber, B Seliger
JournalHuman gene therapy (Hum Gene Ther) Vol. 9 Issue 1 Pg. 53-62 (Jan 01 1998) ISSN: 1043-0342 [Print] United States
PMID9458242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, Neoplasm
  • B7-1 Antigen
  • Genetic Markers
  • HLA-B7 Antigen
  • Histocompatibility Antigens Class I
Topics
  • Antigens, Neoplasm (immunology)
  • B7-1 Antigen (genetics, immunology)
  • Carcinoma, Renal Cell (genetics, therapy)
  • Gene Transfer Techniques
  • Genetic Markers (genetics, immunology)
  • Genetic Therapy (methods)
  • Genetic Vectors (genetics, immunology)
  • HLA-B7 Antigen (immunology)
  • Histocompatibility Antigens Class I (immunology, physiology)
  • Humans
  • Kidney Neoplasms (genetics, therapy)
  • Lymphocyte Activation
  • Retroviridae (genetics)
  • T-Lymphocytes, Cytotoxic (immunology, physiology)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: