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Recombinant vaccinia viruses expressing immunoglobulin variable regions efficiently and selectively protect mice against tumoral B-cell growth
- Source :
- Cancer Gene Therapy. 8:815-826
- Publication Year :
- 2001
- Publisher :
- Springer Science and Business Media LLC, 2001.
-
Abstract
- The variable regions of the immunoglobulin (Ig) expressed on the surface of a malignant B cell can be considered tumor-specific antigens and, as such, could be targets for immunotherapeutic approaches. However, because until now the immunization procedures have been complex and have given only partial protection, it was necessary to find new methods of immunotherapy. Here, we present a successful method of vaccination against B-cell tumors in a murine model. We produced recombinant vaccinia viruses (rVV) expressing the heavy and the light chain of surface Ig of a patient's malignant B cells and we tested the ability of these rVV to protect immunized mice against tumor growth of transfectomas producing the same human Ig. The protection of the mice was complete and specific to the variable region of the immunizing heavy chain although specific lymphoproliferative and cytotoxic responses were not detectable in vitro. The protection was strictly dependent on the presence of CD4 T cells and asialo GM1+ cells. Furthermore, tumor protection clearly required gamma-interferon and was partially inhibited by blocking the Fas-Fas ligand interaction. We also show, in a murine syngeneic model, that rVV expressing a poorly mutated Ig protects against the growth of Ig-producing tumor.
- Subjects :
- CD4-Positive T-Lymphocytes
Cancer Research
Lymphoma, B-Cell
viruses
Genetic Vectors
Molecular Sequence Data
Immunoglobulin Variable Region
Vaccinia virus
G(M1) Ganglioside
law.invention
Interferon-gamma
Mice
Immunoglobulin Idiotypes
law
Cricetinae
medicine
Animals
Humans
Amino Acid Sequence
fas Receptor
Molecular Biology
B cell
Mice, Inbred BALB C
Base Sequence
biology
Vaccination
Neoplasms, Experimental
Flow Cytometry
Virology
Recombinant Proteins
medicine.anatomical_structure
biology.protein
Recombinant DNA
Molecular Medicine
Female
Antibody
Vaccinia viruses
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi.dedup.....b49290b63f952fcebfe8b44843283cda