Preliminary Study With The Pretargeted Immuno-directed Adriamycin On S180 Sarcoma

Background:At present cancer is still has graveness intimidate on human life.Depend on the report the incidence of cancer is increase every year,and the current is become younger.There will has 15 million tumor sufferers all over the world at 2020. Chemotherapy is the most important one of the treatment means to cure cancer.The traditional chemotherapy is across some ways to make the medicine get the chroma at which level can treat cancer.In clinical practice we discovered that after the chemotherapy which directly aimed at the tumor,the tumor was clinical extinctted. However it would recur soon and has high toxicity.Some of the sickliness have severity toxic assistant response,another have low curative effect and may drug resistant.Lately,the international mainstream medical treatment of tumors from the previous mode of "search and destroy" gradual change "targeting and control",that is difficult to cure for the cancer patients for targeted therapy to control the spread and transfer of lesions and improve the lives of patients Quality and prolong its survival.The monoclonal antibody target drug has been the research hotspot of international biology domain.The monoclonal antibody target drug is uses some kinds of substance which has relative with tumor cell as cartier,prepares drug which targets to the abnormal molecule or gene.These drug can selectivity kill the tumor cell moreover without wound the normal cell.The transferation of target drug is overpasses three steps:first make the drug arrive the first target-the apparatus;then arrive the second target-the cells;at last arrive the final target-the structures inside the cell.The effect of the target drug is decided by two aspects:â‘ The speciality of the target drug;â‘¡There are targets and abnormity state inside the tumor which can be combined with the drug.The perfect target has these characteristics:â‘ The target is a very pivotal molecule of the sick.â‘¡The target is not expression in the important apparatus and tissue.â‘¢The target has relative with biology behavior.â‘£The target can be repeating measured.⑤The target has relative with clinic evidence.At present there are many tumor have not find the target for the target treatment.So that find out the new target is the hotspot in the target treatment research.There are many experiments show that inject virus,bacteria which had been gene altered will make the immunity react and will react rapidly when inject them again.The react is much more intensive and kill more tumor cells.The inhibitory rate is ascend.At the same time radiation immunity treatment give a new conception called pretargeted radio immunotherapy.These experiment give us a clue that we can make a artificial target in tumor.This is a new way for tumor treatment.This experiment is use mouse anti-human IgG as carrier conjugate adriarnycin (ADM).Inject human IgG as target in tumor.By binding human IgG with Anti-human IgG make the ADM into tumor.Discuss the possibility of make artificial target for target treatment.Objective:To prepare mouse anti-human IgG-dextran- Adriamycinconjugate,to establish the model of S180 sarcoma in Kunming mouse,and to inject human IgG in sarcoma,by binding human IgG with Anti-human IgG-dextran-ADM.To study the effects of immuno-directed therapy with artifical target.Methods:Human IgG is labbelled with radioactive isotope ¹²⁵I-NaI.Inject ¹²⁵I-NaI and ¹²⁵I- human IgG separately into the sarcoma.Then observe the movement of radioactive isotope at 0,1h,2h,4h,8h,24,48h by ECT.Anti-human IgG-dextran-ADM was synthesized by conjugating dextran,ADM with anti-human IgG.To establish the model of S180 sarcoma in the 90 kunming mice.8 of them were injected in left legs,82 of them were injected into the right back.The cytotoxicity of anti-human IgG,ADM,Anti-human IgG-dextran-ADM were detected by measuring the inhibition of cell growth using the MTT assay.High performance liquid chromatography(HPLC) was performed to measure the ADM concentration in tumor tissue.Moreover,comparing the impact of inhibitory rate and the survival time of ADM,Anti-human IgG-dextran-ADM,Anti-human IgG-dextran-ADM+human IgG in mouse.Result:The tumor-bearing mouse successfully prepared rate is 98.75%.The radioactive counting of tumor region of ¹²⁵I-human IgG group had a significant difference of the ¹²⁵I-NaI group's(P=0.008,0.003,0.000,0.000,0.000,0.006＜0.05).The conjugate was successfully prepared.The molecular ratio of anti-mouse IgG,dextran,Adriamycin was 1:2.5:38.The conjugate retained part of the immunoactivity of anti-humanIgG against the antigen.The conjugates have cytotoxicity to the S180 sarcoma cells.The Ic50 of mouse anti-human IgG-dextran-ADM and ADM had a significant difference(P=0.009＜0.05).The Ic50 of mouse anti-human IgG and ADM had a significant difference(P=0.033＜0.05). The Ic50 of mouse anti-human IgG and mouse anti-human IgG-dextran-ADM had a significant difference(P=0.033＜0.05).The content of the ADM in tumor were detected by HPLC.The density of ADM had a significant difference between group â… and groupâ…¡(P=0.004＜0.01).Mouse anti-human IgG-dextran-ADM+human IgG suppresses the growth of S180 sarcoma transplanted into mice at a rate of 18.13%,which had a significant difference with the other three groups (P=0.018＜0.05,P=0.031＜0.05,P=0.000＜0.05).But could not prolong the life-span of mice which bearing S180 sarcoma.(P=0.959＞0.05,P=0.607＞0.05).Conclusion:The human IgG was injected into tumor as non-specific target could targeting the muse anti-human IgG-dextran-ADM.It is a demonsteation of the possibilty of make a man-made target in the tumor.