Target Density, Not Affinity or Avidity of Antigen Recognition, Determines Adoptive T Cell Therapy Outcomes in a Mouse Lymphoma Model.

Détails

ID Serval
serval:BIB_3F4F7E1C3D10
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Target Density, Not Affinity or Avidity of Antigen Recognition, Determines Adoptive T Cell Therapy Outcomes in a Mouse Lymphoma Model.
Périodique
Journal of immunology
Auteur(s)
Segal G., Prato S., Zehn D., Mintern J.D., Villadangos J.A.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Statut éditorial
Publié
Date de publication
01/05/2016
Peer-reviewed
Oui
Volume
196
Numéro
9
Pages
3935-3942
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Adoptive T cell therapy (ACT) with antitumor CTL is a promising and tailored treatment against cancer. We investigated the role played by the affinity and avidity of the interaction between the tumor and the CTL on the outcome of ACT against a mouse non-Hodgkin B cell lymphoma that expresses OVA as a model neoantigen. ACT was assessed under conditions where antitumor CTL expressed TCR of varying affinity for OVA. We also assessed conditions where the avidity of Ag recognition varied because the lymphoma cells expressed high or low levels of OVA. Efficient eradication of small tumor burdens was achieved by high- or low-affinity CTL. Tumors expressing low levels of OVA could also be eliminated. However, ACT against large tumor burdens was unsuccessful, accompanied by CTL deletion and functional impairment. This negative outcome was not prevented by lowering the affinity of the CTL or the expression of OVA in the lymphoma. Thus, tumor burden, rather than CTL affinity or avidity, appears to be the main determinant of ACT outcomes in our lymphoma model. Insofar as our results can be extrapolated to the clinical setting, they imply that the range of CTL and tumor-associated Ag combinations that may be effectively harnessed in ACT against lymphoma may be wider than generally assumed. CTL expressing low-affinity TCR may be effective against lymphoma, and lowly expressed tumor-associated Ag should be considered as potential targets, but tumor reduction should always be implemented before infusion of the CTL.

Mots-clé
Animals, Antigens/immunology, Antigens/metabolism, Cancer Vaccines/immunology, Cells, Cultured, Cytotoxicity, Immunologic, Dendritic Cells/immunology, Disease Models, Animal, Humans, Immunotherapy, Adoptive/methods, Lymphocyte Activation, Lymphoma/immunology, Lymphoma/therapy, Male, Mice, Mice, Inbred C57BL, Receptors, Antigen, T-Cell/metabolism, T-Lymphocytes, Cytotoxic/immunology, T-Lymphocytes, Cytotoxic/transplantation
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/04/2016 17:40
Dernière modification de la notice
08/05/2019 17:32
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