Escribà-Garcia et al. tested the newly developed agonistic antibody NKT14m, which targets the invariant TCR on iNKT cells, in a mouse model of B cell lymphoma. Early administration of a single dose of NKT14m increased IFNγ production by iNKT cells and mediated a moderate antitumor effect and survival benefit. A second dose of NKT14m restimulated IFNγ+ iNKT cells and further augmented the therapeutic activity. Addition of NKT14m to cyclophosphamide had synergistic activity, increased the percentage of IFNγ-producing iNKT, CD4+, and CD8+ T cells, significantly enhanced survival, and protected some surviving mice from tumor rechallenge.
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 _-galactosylceramide (_-GalCer) triggers innate and adaptive immune responses. The use of _-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-_ 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.