Journal: Journal for Immunotherapy of Cancer
Article Title: Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors
doi: 10.1136/jitc-2021-003050
Figure Lengend Snippet: Pretreatment with Dox and TMZ enhances the in vivo antitumor activity of anti-HLA-G CAR-NK cells. (A) Treatment protocol used for the TNBC animal model. MDA-MB-231 cells (1×10 6 /mouse) were implanted orthotopically on day 0. On day 6 and for the following 3 weeks, mice received a weekly injection of normal saline or 0.5 mg/kg Dox via the tail vein. On day 7, mice were injected with normal saline or with 1.5×10 7 mock or anti-HLA-G CAR-NK cells, followed by infusion of 5×10 6 mock or anti-HLA-G CAR-NK cells each subsequent week for 3 weeks. (B) Representative IVIS images of MDA-MB231 tumors treated according to the protocols described in (A). Images were taken weekly. (C) Tumor progression, as measured by bioluminescence photometry. The luminoscore was calculated as the sum of flux values from the front and back views. (D) Survival was plotted using the Kaplan-Meier method. Mice were considered dead when the tumor volume exceeded 2000 mm 3 or the greatest dimension was >1.5 cm in any direction, as measured using an electronic manual caliper. (E) Treatment protocol for the GBM animal model. U87 cells (1×10 6 /mouse) were implanted intracranially on day 0. On day 6 and for the following 3 weeks, mice were treated weekly (or not) with 3 mg/kg TMZ by oral gavage. Mice were injected with normal saline, or 1.5×10 7 mock or anti-HLA-G CAR-NK cells, on day 7, followed by infusion of 5×10 6 mock or anti-HLA-G CAR-NK cells each subsequent week for 3 weeks. (F) Representative weekly IVIS images of U87 tumors treated according to the protocols described in (E). (G) Tumor progression, as measured by bioluminescence photometry. (H) Survival plotted using the Kaplan-Meier method (*p<0.05, **p<0.01, ***p<0.001). CAR, chimeric antigen receptor; Dox, doxorubicin; GBM, glioblastoma; HLA-G, human leukocyte antigen G; IL, interleukin; NK, natural killer; TMZ, temozolomide; TNBC, triple-negative breast cancer.
Article Snippet: The Luc-expressing human glioblastoma (GBM) cell line U87 MG-Luc2 (ATCC) and SVGp12 (ATCC) were cultured in Eagle’s minimal essential medium (Thermo Fisher Scientific).
Techniques: In Vivo, Activity Assay, Animal Model, Injection, Saline