Therapeutic Effects Of IN Combination With Anti-PD-1 On Various Tumor Models In Mice

Background: Anti-PD-1 antibody has anti-tumor activity and the potential of treating various cancer,but Anti-PD-1 may produce many side effects.Many patients do not respond to the drug,and the response is short.The immunotherapy of PD-1 antibody combined with other drugs can reduce its toxicity and side effects,increase and prolong the anti-tumor response.Objective: To evaluate the therapeutic effects of IN combination with Anti-PD-1 on various tumor models,12 different tumor models were established.Method: To establish cancer models,different cell lines were injected to the BALB/C and C57BL/6 mouse.The established tumor models included CT26 tumor model,H22 tumor model,PAN02 tumor model,B16BL6 tumor model,RM-1 tumor model,RENCA tumor model,B16F10 tumor model,MC38 tumor model,HEPA1-6 tumor model,LL/2tumor model,A20 tumor model,EMT-6 tumor model.Then the tumor models were randomly divided into 3 groups(n=10): Negative control group(PBS group),Anti-PD-1group,Anti-PD-1+IN group.In order to reduce the error caused by the drug batches,the H22 model received two drugs(665418F1 and 665418J1).The H22 tumor models were divided into 5 groups:(1)Negative control group(PBS group);(2)Anti-PD-1(F)group;(3)Anti-PD-1(F)+ IN group;(2)Anti-PD-1(J)group;(3)Anti-PD-1(J)+ IN group.Dosing,tumor and body weight measurements were performed in a laminar flow cabinet every week.We measured tumor volume and mouse body weight every week.Results:(1)When Anti-PD-1 was alone used to treat CT26 colon cancer model,MC38 colon cancer model,A20 lymphoma model and EMT-6 breast cancer model,the tumor inhibition rate of Anti-PD-1 were more than 40 %.However,the tumor inhibition rate of MC38 colon cancer model was the highest(58.71 %,p<0.001)and the efficacy of Anti-PD-1 was higher than that of IN combination with Anti-PD-1.But Anti-PD-1 did not inhibit tumor growth of B16F10 melanoma cancer model,PAN02 pancreatic cancer model and RM-1 prostate cancer model.(2)The treatment of IN combination with Anti-PD-1 had a higher tumor inhibition rate in H22 liver cancer model,HEPA1-6 liver cancer cell model,PAN02 pancreatic cancer model and RM-1 prostate cancer model,especially the H22 liver cancer model,the tumor suppression rate was 41.97 %(P<0.01).(3)In the repeated experiment of H22 model,the tumor inhibition rate of the Anti-PD-1(F)+IN group and Anti-PD-1(J)+IN group were 49.5 %(P <0.001)And 63.11 %(P <0.01),respectively,and the efficacy of the two groups were higher than Anti-PD-1 group.(4)Among all the tested mice,only 5 mice died and all treatment methods could be tolerated by the tumor-bearing mice.Conclusion: Among the tested 12 models,Anti-PD-1 is alone use to treat CT26 colon cancer model,MC38 colon cancer model,A20 lymphoma cancer model and EMT-6 breast cancer model more effective than Anti-PD-1+IN group.The efficacy of Anti-PD-1+IN group in H22 liver cancer model is significantly higher than that in Anti-PD-1 group.However,IN and Anti-PD-1 have a synergistic effect,and IN drug seem to increase the efficacy of Anti-PD-1,which is useful and has great potential for improving the efficacy of liver cancer patients in clinical treatment.