An optimum anti-melanoma response in mice immunized with fibroblasts transfected with DNA from mouse melanoma cells requires the expression of both syngeneic and allogeneic MHC-determinants
| Autor: | E F de Zoeten, Edward P. Cohen, D Markovic |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Melanoma
Experimental chemical and pharmacologic phenomena Transfection Major histocompatibility complex Cell Line Cell therapy Epitopes Mice Immune system Genetics medicine Animals Fibroblast neoplasms Molecular Biology Mice Inbred C3H biology Melanoma Histocompatibility Antigens Class I Genetic transfer DNA Neoplasm Genetic Therapy Fibroblasts medicine.disease Mice Inbred C57BL medicine.anatomical_structure Cell culture Immunology Cancer research biology.protein Molecular Medicine Female Immunotherapy |
| Zdroj: | Gene Therapy. 9:1163-1172 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | Most neoplasms do not induce antitumor immune responses that can control tumor growth. Tumor associated antigens (TAAs) are insufficiently immunogenic. A vaccine that augments the immunogenic properties of TAAs could be of importance in the treatment of cancer patients. In an animal model, we prepared a vaccine by transfection of highly antigenic allogeneic mouse fibroblasts (LM; H-2(k)) with DNA from B16 mouse melanoma cells. We then tested the transfected cells' immunogenic properties in C57BL/6 mice, syngeneic with the melanoma (H-2(b)). We hypothesized that the immunogenic properties of 'weak' TAAs formed by the neoplasm would be enhanced if they were expressed by highly antigenic cells. The results indicated that mice with melanoma treated by immunization with the DNA-transfected fibroblasts survived significantly longer than mice in various control groups. To investigate the contribution of MHC determinants expressed by the transfected cells to their immunogenic properties, we compared the antimelanoma responses in mice immunized with transfected cells that expressed allogeneic or syngeneic class I determinants. The results indicated that the immunogenic properties of the DNA-transfected cells were enhanced if the cells expressed allogeneic MHC determinants. The antimelanoma responses of greatest magnitude, however, mediated predominantly by CD8(+) T cells, were in mice immunized with transfected fibroblasts that expressed both syngeneic and allogeneic class I determinants. |
| Databáze: | OpenAIRE |
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