Researches Of Targeted Blockade Immune-Checkpoint Molecule CEACAM1 Suppress Glioma

Objective : To study targeted blocking immune checkpoint CEACAM1 suppressing intracranial glioma proliferation in mice and the influence of the anti-tumor immunity ability.Method : Utilizing the slow virus with luciferase gene and puro resistance to transfect GL261 mice glioma cell line, with stereotactic technique to C57BL/6 mice implanted glioma cells on the right side of the caudate nucleus, construct the intracranial glioma model in mice. Then utilizing small living animal imaging technology to observe the Tumor growth in mice. Averagely divided the mice into treatment group and control group according to size of the tumors. Tumor mice according to size of the tumors had an average can be divided into treatment group and control group, given intraperitoneal injection of CEACAM1 monoclonal antibody or equivalent sterile PBS, then to observe the effects of intracranial glioma growthing, recorded survival, drawn survival curve; Collected the tumor, spleen, peripheral blood, HE staining, immunohist-ochemical staining(PCNA),Flow cytometry to detect the level of CD8 + T cells in the spleen, Elisa to measure the levels of mice peripheral blood TGF-?.Result : 1.After puro screening GL261 mice glioma cells, cell morphology is normal,growth in good condition; 2. Intracranial glioma model in mice constructed successfully,rate of tumor formation up to 80%; 3.Treatment group of intracranial tumors in mice average volume was 0.125 ± 0.009cm3, and control group was 0.361 ± 0.0017cm3;4.Average survival period of treatment group was 55.1±3.8d, and control group was 34.7±2.6d; 5. HE staining results confirmed for glioma tumor, the growth characteristics and pathologic characteristics was similar to human brain gliomas;6.Immunohistochemical staining results show that the PCNA expression was reduced in treatment group, but increased in control group; 7.Flow cytometry results showed that the CD8+T cells was increased in mice spleen of treatment group;8. ELISA results indicated that the serum TGF-?of treatment group were significantly lower than the control group.Conclusion : Growth characteristics and pathological features of intracranial glioma model in mice is similar to the human brain glioma, can extremely simulat the microenvironment and immunological characteristics of human brain glioma tumor;targeted blocking CEACAM1 can obviously inhibit the growth of intracranial glioma in mice, and enhance the antitumor immunity ability of mice.