Evaluation of I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice.
10.1016/j.apsb.2020.02.004
- Author:
Haifeng HUANG
1
;
Hua ZHU
2
;
Quan XIE
1
;
Xiaobin TIAN
1
;
Xianteng YANG
1
;
Fan FENG
3
;
Qiyu JIANG
3
;
Xinan SHENG
4
;
Zhi YANG
2
Author Information
1. Guizhou University School of Medicine, Guizhou University, Guiyang 550025, China.
2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
3. Research Center for Clinical and Translational Medicine, the 302nd Hospital of Chinese PLA, Beijing 100039, China.
4. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing 100142, China.
- Publication Type:Journal Article
- Keywords:
CTLA4, cytotoxic T lymphocyte-associated antigen 4;
HAS, human serum albumin;
ICI, immune checkpoint inhibitor;
IHC, immunohistochemistry;
Immuno-PET imaging;
Immunotherapy;
Iodine isotopes;
JS001;
NMPA, National Medical Products Administration;
OSEM, ordered subsets expectation maximum;
PB, phosphate buffer;
PBMCs, peripheral blood mononuclear cells;
PBS, phosphate buffered saline;
PCR, polymerase chain reaction;
PD1, programmed cell death protein 1;
PDL1, programmed cell death ligand 1;
PHA, phytohemagglutinin;
Programmed cell death protein 1;
SCLC, small-cell lung cancer;
Toripalimab
- From:
Acta Pharmaceutica Sinica B
2020;10(7):1321-1330
- CountryChina
- Language:English
-
Abstract:
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 (I) to label JS001 probes to target the human PD1 (hPD1) antigen. , the half maximal effective concentration (EC) value of I-JS001 did not significantly differ from that of JS001. The uptake of I-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 I-JS001 to T cells of different lineages after phytohemagglutinin (PHA) stimulation reached 4.26 nmol/L. Humanized C57BL/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 Ihuman IgG (IhIgG) group or blocking group was used as a control group. Immuno-PET imaging showed that the uptake in the tumor area of the I-JS001 group at different time points was significantly higher than that of the blocking group or the I-hIgG group in the humanized 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.
