Format

Send to

Choose Destination
Oncoimmunology. 2018 Nov 26;8(2):e1546543. doi: 10.1080/2162402X.2018.1546543. eCollection 2019.

The novel agonistic iNKT-cell antibody NKT14m induces a therapeutic antitumor response against B-cell lymphoma.

Author information

1
Hematology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
2
Laboratory of Experimental Hematology-IIB, Institut Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
3
Josep Carreras Leukaemia Research Institute, Barcelona, Spain.
4
NKT Therapeutics Inc, Sharon, MA (USA).
5
Autonomous University, Barcelona, Spain.

Abstract

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 α-galactosylceramide (α-GalCer) triggers innate and adaptive immune responses. The use of α-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-γ 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.

KEYWORDS:

B-cell lymphoma; Inkt cells; NKT14m; antibody; immunotherapy

PMID:
30713807
PMCID:
PMC6343796
[Available on 2019-11-26]
DOI:
10.1080/2162402X.2018.1546543

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center