Evaluation of 124I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice

Haifeng Huang; Hua Zhu; Quan Xie; Xiaobin Tian; Xianteng Yang; Fan Feng; Qiyu Jiang; Xinan Sheng; Zhi Yang

doi:10.1016/j.apsb.2020.02.004

Evaluation of ¹²⁴I-JS001 for hPD1 immuno-PET imaging using sarcoma cell homografts in humanized mice

Acta Pharm Sin B. 2020 Jul;10(7):1321-1330. doi: 10.1016/j.apsb.2020.02.004. Epub 2020 Feb 19.

Authors

Haifeng Huang^{1

2}, Hua Zhu³, Quan Xie¹, Xiaobin Tian¹, Xianteng Yang^{1

2}, Fan Feng⁴, Qiyu Jiang⁴, Xinan Sheng⁵, Zhi Yang³

Affiliations

¹ Guizhou University School of Medicine, Guizhou University, Guiyang 550025, China.
² Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, China.
³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, China.
⁴ Research Center for Clinical and Translational Medicine, the 302nd Hospital of Chinese PLA, Beijing 100039, China.
⁵ 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.

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 (^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 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 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.

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.