JS001(toripalimab)is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1(PD1).In this study,we used a different iodine isotype(nat/124/125I)to label JS001 probes to target the h...JS001(toripalimab)is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1(PD1).In this study,we used a different iodine isotype(nat/124/125I)to label JS001 probes to target the human PD1(hPD1)antigen.In vitro,the half maximal effective concentration(EC50)value of natI-JS001 did not significantly differ from that of JS001.The uptake of 125I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation.The binding affinity of 125I-JS001 to T cells of different lineages after phytohemagglutinin(PHA)stimulation reached 4.26 nmol/L.Humanized PD1 C57 BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography(immuno-PET)imaging.Pathological staining was used to assess the expression of PD1 in tumor tissues.The homologous 124I-human IgG(124I-hIgG)group or blocking group was used as a control group.Immuno-PET imaging showed that the uptake in the tumor area of the 124I-JS001 group at different time points was significantly higher than that of the blocking group or the 124I-hIgG group in the humanized PD1 mouse model.Taken together,these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.展开更多
基金financially supported by the National Natural Science Foundation of China(81960538,81571705,81671733,81871386,81560356,61264004 and 81871387)the Beijing Nova Program(Z171100001117020,China)+4 种基金the Beijing Excellent Talents Funding(2017000021223ZK33,China)the Beijing Municipal Science&Technology Commission(Z161100000516062,China)Open Project funded by Key laboratory of Carcinogenesis and Translational Research,Ministry of Education/Beijing(2017 open project-1 and 2019 open project-06,China)High-level Creative Talent Training Program in Guizhou Province of China(Grant No.[2015]4015)the Science and Technology Foundation of Guizhou Province(No.gzwjkj2018-1-040 and no.[2019]1201,China)
文摘JS001(toripalimab)is a humanized IgG monoclonal antibody which strongly inhibits programmed cell death protein 1(PD1).In this study,we used a different iodine isotype(nat/124/125I)to label JS001 probes to target the human PD1(hPD1)antigen.In vitro,the half maximal effective concentration(EC50)value of natI-JS001 did not significantly differ from that of JS001.The uptake of 125I-JS001 by activated T cells was 5.63 times higher than that by nonactivated T cells after 2 h of incubation.The binding affinity of 125I-JS001 to T cells of different lineages after phytohemagglutinin(PHA)stimulation reached 4.26 nmol/L.Humanized PD1 C57 BL/6 mice bearing mouse sarcoma S180 cell tumors were validated for immuno-positron emission tomography(immuno-PET)imaging.Pathological staining was used to assess the expression of PD1 in tumor tissues.The homologous 124I-human IgG(124I-hIgG)group or blocking group was used as a control group.Immuno-PET imaging showed that the uptake in the tumor area of the 124I-JS001 group at different time points was significantly higher than that of the blocking group or the 124I-hIgG group in the humanized PD1 mouse model.Taken together,these results suggest that this radiotracer has potential for noninvasive monitoring and directing tumor-specific personalized immunotherapy in PD1-positive tumors.
