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Anti-Gal-mediated targeting of human B lymphoma cells to antigen-presenting cells: a potential method for immunotherapy using autologous tumor cells.

Olivier Manches 1 Joël Plumas 2, * Gabrielle Lui 1 Laurence Chaperot 1 Jean-Paul Molens 1 Jean-Jacques Sotto 1 Jean-Claude Bensa 1 Uri Galili 3
* Corresponding author
2 INSERM U823, équipe 9 (Immunobiologie et Immunothérapie des Cancers)
INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble, Laboratoire recherche et développement
Abstract : BACKGROUND AND OBJECTIVES: The residual tumor cells remaining after completion of standard chemotherapy and radiation treatment in B lymphoma patients, may be eradicated by active immunotherapy that stimulates tumor-specific T lymphocytes. Irradiated autologous lymphoma cells expressing tumor-associated antigens (TAA) may serve as a potential tumor vaccine, provided that they are effectively targeted to the antigen-presenting cells (APC). We propose exploiting the natural anti-Gal antibody in order to target vaccinating tumor cells to APC. Anti-Gal constitutes 1% of IgG in human serum and interacts specifically with the alpha-gal epitope (Galalpha1-3Galphalbeta1-4GlcNAc-R). DESIGN AND METHODS: Alpha-gal epitopes were synthesized in vitro on the membrane of primary lymphoma cells by using the recombinant glycosylation enzyme alpha1,3galactosyltransferase (alpha1,3GT). Processed tumor cells were opsonized by purified anti-Gal antibodies and studied for uptake (phagocytosis) by APC including monocyte-derived macrophages and dendritic cells. Cross-presentation of tumor antigens after phagocytosis of processed MHC-I negative lymphoma cells was measured by activation of a tumor-specific CD8+ T-cell line. RESULTS: We demonstrate synthesis of alpha-gal epitopes on freshly isolated B lymphoma cells of various types following the use of the recombinant enzyme alpha1,3GT. The subsequent binding of anti-Gal to the de novo synthesized alphagal epitopes opsonizes these tumor cells for effective uptake by macrophages and dendritic cells, through phagocytosis mediated by FcgammaR1 (CD64). Moreover, anti-Gal-mediated phagocytosis resulted in cross-presentation of TAA by dendritic cells. INTERPRETATION AND CONCLUSIONS: This study suggests that immunization with irradiated autologous lymphoma cells processed to express alpha-gal epitopes will result in anti-Gal-mediated, in vivo targeting of the autologous tumor vaccine to APC.
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https://www.hal.inserm.fr/inserm-00286462
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Submitted on : Tuesday, December 28, 2010 - 1:05:08 PM
Last modification on : Friday, November 6, 2020 - 4:15:34 AM
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  • HAL Id : inserm-00286462, version 1
  • PUBMED : 15921377

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Olivier Manches, Joël Plumas, Gabrielle Lui, Laurence Chaperot, Jean-Paul Molens, et al.. Anti-Gal-mediated targeting of human B lymphoma cells to antigen-presenting cells: a potential method for immunotherapy using autologous tumor cells.. Haematologica, Ferrata Storti Foundation, 2005, 90 (5), pp.625-34. ⟨inserm-00286462⟩

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