Superior tumor protection induced by a cellular vaccine carrying a tumor-specific T helper epitope by genetic exchange of the class II-associated invariant chain peptide
| Autor: | van Bergen J, Camps M, Offringa R, Cj, Melief, Ossendorp F, Frits Koning |
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| Předmět: |
Antigen Presentation
Mice Inbred BALB C Molecular Sequence Data Retroviridae Proteins Oncogenic Vaccination Histocompatibility Antigens Class II Antigen-Presenting Cells Epitopes T-Lymphocyte T-Lymphocytes Helper-Inducer Lymphocyte Activation Lymphoma T-Cell Transfection Cancer Vaccines Antigens Differentiation B-Lymphocyte Mice Inbred C57BL Mice Viral Envelope Proteins Antigens Neoplasm Animals Female Amino Acid Sequence |
| Zdroj: | Europe PubMed Central |
| Popis: | Efficient loading of MHC class II molecules with a T helper epitope of choice can be achieved through genetic exchange of the MHC class II-associated invariant chain peptide (CLIP) sequence with a sequence encoding the helper peptide. We have now used this method to engineer a cellular vaccine that continuously expresses a tumor-specific helper epitope in a defined costimulatory context. We provide evidence (a) that this cellular vaccine induces peptide-specific helper T cells in vivo that are functional in protecting mice from challenge with a highly aggressive tumor, (b) that this vaccine can directly prime tumor-specific helper T cells in vivo, and (c) that this cellular vaccine is superior compared with similar cells loaded with synthetic T helper peptide in inducing tumor protection. In conclusion, cellular vaccines for activation of antigen-specific helper T cells can be greatly improved by the introduction of invariant chain constructs containing a T helper epitope by class II-associated invariant chain peptide exchange. |
| Databáze: | OpenAIRE |
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