[Dendritic cells and tumor cell therapy].
Antigen presentation to T lymphocytes appears to be one of the deficient step in the induction of anti-tumoral immune responses. To overcome this deficit, it should be possible to use the professional antigen presenting dendritic cells. The principle of this strategy would be to purify dendritic cells, to prime them ex vivo with tumoral antigen, and to re-inject them to patient. The purification of dendritic cells can be achieved from the spleen, bone marrow, and peripheral or cord blood. Their sensitization to tumoral antigen could be obtained using various antigeneic preparation such as crude tumoral extract, or purified antigen, that will lead to an MHC class II restricted antigenic presentation to CD4+ T cells. Gene transfer can be used in the case of a cloned antigen and would lead to the restricted MHC class I priming of CD8+ T cells. The mode of administration, the nature of the dendritic cells used, the number of sensitized cells to inject, might depend on the nature and the location of the tumour. In vitro, it has been shown that dendritic cells sensitized with tumoral antigen are capable of triggering proliferative immune responses as well as cytotoxic T cells. In vivo, injection of dendritic cells primed with tumour cell lysate leads to protection of mice against a tumour challenge. Finally, gene transfer to dendritic cells is shown hereby to be possible, although the efficacy of transduction is still very low, and must be improved. Altogether, it should soon be feasible to use ex vivo primed dendritic cells for triggering otherwise inefficient immune responses in pathologies such as cancer or HIV infection.
Pioche
C
C
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Hôpital de la Pitié, Paris, France.
Salomon
B
B
Klatzmann
D
D
D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
D000951:Antigens, Neoplasm; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
Cellules dendritiques et thérapie cellulaire antitumorale.