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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Potential immunogenicity of oncogene and tumor suppressor gene products
1Department of Immunohaematology and Bloodbank, University Hospital Leiden, The Netherlands.
Abstract:
The immunogenicity of viral oncoproteins has been established beyond doubt. Cytotoxic T lymphocytes directed against viral oncogene products can eradicate large established tumor masses. This stage has not yet been reached for cellular oncogene and tumor suppressor gene products, but T cells have been raised against MHC-binding peptides encoded by both mutant and wild-type alleles of the ras oncogene and the p53 tumor suppressor gene. In addition, T cells specific for joining region peptides of abnormal fusion proteins resulting from chromosome translocation in tumor cells have been generated. Some of these peptides are processed in cells infected with, for example, vaccinia-ras, but direct anti-tumor effects of peptide specific T lymphocytes remain to be demonstrated.
Insights
Immune responses targeting viral oncoproteins are effective against tumors. Researchers are developing T-cell therapies against cellular oncogenes and tumor suppressor genes for cancer treatment.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Viral oncoproteins are immunogenic, and cytotoxic T lymphocytes (CTLs) targeting them can eliminate tumors.
- Therapeutic strategies targeting cellular oncogenes and tumor suppressor genes are less advanced but show promise.
Purpose of the Study:
- To explore the potential of T-cell responses against cellular oncogene and tumor suppressor gene products.
- To investigate the generation of T cells specific for tumor-associated antigens, including fusion proteins.
Main Methods:
- Generating T cells against MHC-binding peptides from mutant and wild-type ras oncogene and p53 tumor suppressor gene alleles.
- Generating T cells specific for joining region peptides of tumor-specific fusion proteins resulting from chromosomal translocations.
- Processing peptides in cells infected with viral vectors (e.g., vaccinia-ras).
Main Results:
- T cells have been successfully raised against peptides from ras and p53 genes.
- T cells specific for fusion protein peptides have also been generated.
- Peptide processing in infected cells was demonstrated.
Conclusions:
- While T cells can be generated against tumor-associated peptides from cellular oncogenes, tumor suppressor genes, and fusion proteins, their direct anti-tumor effects require further demonstration.
- This research lays the groundwork for developing novel T-cell-based cancer immunotherapies targeting intracellular tumor antigens.
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