Antibody-dependent cellular cytotoxicity (ADCC) is mediated by genetically modified antigen-specific human T lymphocytes.
In the context of transplantation, donor and virus-specific T-lymphocyte infusions have demonstrated the dramatic potential of T cells as immune effectors. Unfortunately, most attempts to exploit the T-cell immune system against nonviral malignancies in the syngeneic setting have been disappointing. In contrast, treatments based on monoclonal antibodies (Abs) have been clinically successful and have demonstrated the clinical relevance of several antigens as therapeutic targets and the importance of the antibody-dependent cellular cytotoxicity (ADCC) pathway. In the present study, we considered the possibility of arming specific T cells with a receptor that would enable them to mediate ADCC. After transduction with a CD16/gamma receptor gene, CD4(+) and CD8(+) cytotoxic T lymphocytes displayed stable expression of the CD16 receptor at their surface. In the absence of Ab, CD16/gamma expression did not affect the capacity of specific T lymphocytes to kill their target following "natural" T-cell receptor recognition. When tested against the autologous B-lymphoblastoid cell line (BLCL) coated with anti-CD20 mAb, the newly expressed Fc receptor enabled the T cells to kill the BLCL through ADCC. Adoptive transfer of such newly designed immune effector may be considered to increase antibody efficiency by harnessing the immune potential of T cells.
Clémenceau
Béatrice
B
Institut National de la Santé et de la Recherche Médicicale (INSERM) U601, Centre Hospitalier Universitaire de Nantes, 44093 Nantes cedex, France.
Congy-Jolivet
Nicolas
N
Gallot
Géraldine
G
Vivien
Régine
R
Gaschet
Joëlle
J
Thibault
Gilles
G
Vié
Henri
H
D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins; D006801:Humans; D017710:Lymphocyte Transfusion; D017452:Receptors, IgG / Q000235:genetics* / Q000276:immunology; D014161:Transduction, Genetic; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy
D000941:Antigens; D015703:Antigens, CD; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG