Application of DPCPX inhibitor in preparation of PD-L1/PD-1 monoclonal antibody tumor immunotherapy drug
A technology of PD-L1 and anti-tumor immunity, which is applied in the field of PD-L1/PD-1 monoclonal antibody tumor immunotherapy and biology, and can solve problems such as unclear mechanism of action
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Embodiment 1
[0039] 1. In vivo study on the proliferation of adenosine receptor ADORA1 combined with PD-1 monoclonal antibody against transplanted tumor (melanoma) in mice.
[0040] 1.1 Group settings:
[0041] Scramble+IgG2a (control group)
[0042] shAdora1+IgG2a (Adora1 knockdown group)
[0043] Scramble+PD-1mAb (PD-1 mAb treatment group)
[0044] shAdora1+PD-1mAb (joint intervention group)
[0045] 1.2 Experimental process, see figure 1 A:
[0046] About 6 days before the experiment: 6-8 weeks old C57BL / 6 mice were subcutaneously injected with B16F10 melanoma shAdora1 knockdown cell line 5*10 in the right dorsal wing. 5 20 mice each and the same number of Scramble cell lines (control group).
[0047] Day 0 of the experiment: record the body weight and tumor volume of the mice, when the tumor volume grows to about 100mm 3 Beginning at the beginning of time, the mice inoculated with the shAdora1 knockdown cell line and the Scramble cell line were injected intraperitoneally with PD...
Embodiment 2
[0063] 1. The in vivo study of the specific inhibitor DPCPX targeting and inhibiting the proliferation of adenosine receptor ADORA1 combined with PD-1 monoclonal antibody transplanted tumors (melanoma, non-small cell lung cancer) in mice.
[0064] 1.1 Group settings:
[0065] Vehicle+IgG2a (control group)
[0066] DPCPX+IgG2a (Adora1 inhibition group)
[0067] Vehicle+PD-1mAb (PD-1 mAb treatment group)
[0068] DPCPX+PD-1mAb (joint intervention group)
[0069] 1.2 Experimental process, see image 3 A. 4A:
[0070] About 6 days before the experiment: 6-8 weeks C57BL / 6 mice were subcutaneously injected with B16F10 melanoma 5*10 in the right dorsal wing 5 Individual or LLC non-small cell lung cancer 1*10 6 wild-type cell lines, 40 mice each.
[0071] Day 0 of the experiment: record the body weight and tumor volume of the mice, when the tumor volume grows to about 100mm 3 At the beginning of time, the inoculated mice were divided into four groups, respectively, DPCPX 1mg / K...
Embodiment 3
[0093] 1. In vivo study of gene knockdown of transcription factor ATF3 combined with adenosine receptor ADORA1 specific inhibitor DPCPX against proliferation of mouse xenograft tumors (melanoma, non-small cell lung cancer).
[0094] 1.1 Group settings:
[0095] Scramble+vehicle (control group)
[0096] Scramble+DPCPX (Adora1 inhibition group)
[0097] ShAtf3+vehicle (Atf3 knockdown group)
[0098] ShAtf3+DPCPX (joint intervention group)
[0099] 1.2 Experimental process, see Figure 5 A. 6A:
[0100] About 6-8 days before the experiment: 6-8 weeks old C57BL / 6 mice were subcutaneously injected with B16F10 melanoma shAtf3 knockdown cell line 5*10 in the right dorsal wing respectively. 5 Individual or LLC non-small cell lung cancer shATF3 knockdown cell line 1*10 6 , and the same number of Scramble cell lines (control group), 20 mice each.
[0101] Day 0 of the experiment: record the body weight and tumor volume of the mice, when the tumor volume grows to about 100mm 3 Be...
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