The novel agonistic iNKT-cell antibody NKT14m induces a therapeutic antitumor response against B-cell lymphoma
Por:
Escriba-Garcia, L, Alvarez-Fernandez, C, Caballero, AC, Schaub, R, Sierra, J, Briones, J
Publicada:
1 ene 2019
Resumen:
Invariant natural killer T (iNKT) cells are a small population of T lymphocytes that expresses an invariant T cell receptor with a unique specificity for glycolipid antigens. Their activation using the glycolipid alpha-galactosylceramide (alpha-GalCer) triggers innate and adaptive immune responses. The use of alpha-GalCer in preclinical models as a single antitumor treatment showed moderate effect, but its efficacy in cancer patients was less effective. In addition, this glycolipid induces long-term iNKT-cell anergy precluding the possibility of retreatment. Recently, the first murine iNKT-cell agonistic antibody, NKT14m, has been developed. Here, we analyzed, for the first time, the antitumor efficacy of NKT14m in a B-cell lymphoma model. In a therapeutic setting, a single dose of NKT14m had a moderate antitumor efficacy that was associated with an increase of IFN-gamma producing iNKT cells even after a second dose of the NKT14m antibody. Importantly, the combination of a single dose of NKT14m with cyclophosphamide had a potent antitumor efficacy and long-lasting immunity in vivo. Our findings provide the first evidence of the in vivo antitumor efficacy of NKT14m antibody, showing that, either alone or in combination with chemotherapy, induces an effective antitumor response. These results open new opportunities for iNKT-cell mediated immunotherapy to treat B-cell lymphoma.
Filiaciones:
Escriba-Garcia, L:
Hosp Santa Creu & Sant Pau, Hematol Serv, Mas Casanovas 90, Barcelona 08041, Spain
Inst Recerca Hosp Santa Creu & St Pau, Lab Expt Hematol IIB, Barcelona, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Alvarez-Fernandez, C:
Hosp Santa Creu & Sant Pau, Hematol Serv, Mas Casanovas 90, Barcelona 08041, Spain
Inst Recerca Hosp Santa Creu & St Pau, Lab Expt Hematol IIB, Barcelona, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Caballero, AC:
Hosp Santa Creu & Sant Pau, Hematol Serv, Mas Casanovas 90, Barcelona 08041, Spain
Inst Recerca Hosp Santa Creu & St Pau, Lab Expt Hematol IIB, Barcelona, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Schaub, R:
NKT Therapeut Inc, Sharon, MA USA
Sierra, J:
Hosp Santa Creu & Sant Pau, Hematol Serv, Mas Casanovas 90, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Autonomous Univ Barcelona, Barcelona, Spain
Briones, J:
Hosp Santa Creu & Sant Pau, Hematol Serv, Mas Casanovas 90, Barcelona 08041, Spain
Inst Recerca Hosp Santa Creu & St Pau, Lab Expt Hematol IIB, Barcelona, Spain
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Autonomous Univ Barcelona, Barcelona, Spain
Bronze, Green Published
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