As a targeted drug,monoclonal antibodies have been successful in tumor therapy. Thus,antibodies and related products are the fastest-developing biological agents. There are currently more than 40 monoclonal antibodies in the market that have been approved by the FDA,half of which are used to treat cancer. In recent years,a new generation of antibody drugs,such as human anti?body,glyco-engineered antibody,bispecific antibody,antibody-drug conjugates and immune check?point blockade antibody,have successfully cured various malignant tumors. In this paper,the history of antibody treatment for cancer,and the development and prospect of anti-tumor antibodies have been reviewed.

Objective:To locate the region of antigenic epitopes recognized by monoclonal antibody(Z8) against human tumor necrosis factor ?(hTNF ?).Methods:Several recombinant fusion expression vectors were constructed which contained hTNF ? mutant genes deleted different parts respectively. After induction with IPTG, the fusion proteins were expressed and analyzed by SDS PAGE and Western blot.Results:Z8 specially recognized the fusion products which contained amino acids from 92 to 157 of hTNF ?, but not GST and its fusion protein with amino acids from 1 to 91 of hTNF ?.Conclusion:The antigenic epitopes recognized by Z8 were located in the sequence region 92 157 of hTNF ?.

As a new identified help T cell lineage different from Th1 and Th2 cells, Th17 cell has been found played important roles in the pathogenesis of autoimmunity and inflammatory disease. To further identify their roles, the differentiation and regulation of Th17 cells has been widely explored recently. Now it has been confirmed that TGF-beta, combined with IL-6 or IL-21, play critical roles in the differentiation of Th17 cells. While IL-23 mainly contribute in promoting the secretion of IL-17 and maintaining the function of Th17 cells. Corresponding with the Th1,Th2, and Treg cells, which has special transcription factors T-bet、GATA3、Foxp3 respectively, now it has been confirmed that ROR-?t(retinoid-related orphan receptors-?t) is the special transcription factor which specially regulate the differentiation of Th17 cells. Th17 cells function through their secreted pro-inflammatory cytokines, including IL-17A, IL-17F, IL-21, IL-22, IL-6, TNF-?. Among them IL-21,which act as a autocrine cytokine of Th17 cells, play critical roles in promoting the differentiation of Th17 cells while inhibiting the differentiation and function of Th1 and Treg cells. On the other hand, IL-2, which is obligatory for the growth of Th1,Th2,Treg and CD8+T cells, now has been found negatively regulate the differentiation of Th17 cells. In all, differentiation of Th17 and Treg,Th1 cells are exactly regulated in vivo, in which TGF-beta played critical roles. As both Th1 and Th17 cells participate in the pathogenesis of autoimmunity and inflammatory diseases, are they play synergistic roles or function at different time point or location? How TGF-? regulate Th17 and Treg cells?Can Th17 cells be used as a target for immune tolerance induction? All above questions will certainly be of continuing interest.

Biosecurity is an important component of national security and an important guarantee for national revival and the realization of China's dream.However China is facing increasingly serious biological threats .Biosecurity capability build-ing has some problem .For exanyple ,people have a vague idea about the relationship between different biological threats ,the duties and rights of civil-military integration development , the balance between sustainable development and emergency pre-vention and control capacity-building, multidisciplinary convergence of biosecurity capacity-building, and about ways to break down the technological blockade and market monopoly by the United States and other developed countries .

Objective　To investigate the IL-6 signal transduction pathways and their regulation mechanism in a human myeloma cell line-U266. Methods　Electrophoretic mobility shift assay (EMSA) was used to detect the activation of the transcription factors (TFs)-STAT3 and NF-IL-6 by IL-6. Cells were treated with chemical agents or transfected with the expression plasmids for the two TFs or the anti-sense oligonucleotide for protein kinase involved in one IL-6 signal transduction pathway. The change of the activation state of another IL-6 signal transduction pathway was also exhibited by EMSA. Results　Two IL-6 signal transduction pathways (JAK/STAT and Ras/NF-IL-6) can be activated by IL-6 of different dose in U266 cells. When one of the two signal transduction pathways was up-regulated, the other one was down-regulated. Conclusion　There is an antagonistic effect between the activation of two IL-6 signal transduction pathways in U266 cells.

Aim To investigate the signaling basis of the biological effects of IL-6 in U937 cells. Methods We determined the effect of IL-6 on the growth and differentiation of U937 cells and the effect of IL-6 on the activation of nuclear factors in U937 cells. Results IL-6 induced macrophage differentiation of U937 cells. Differentiated cells had strengthened ANAE (acid naphthyl acetate esterase)and NBT(nitroblue tetrazolium)-reducing activities and CD54 expression was upregulated. STAT3 could be remarkably activated by IL-6 in U937 cells and STAT3 activity was dependent on dose and time course of IL-6 treatment. However, NF-IL6,NF-κ B, AP-1 and other STAT members were not activated by IL-6. Conclusion IL-6 might induce terminal differentiation of U937 cells via JAK-STAT3 pathway.

Bone marrow transplantation was considered effective treatment for leukemias and other haematological diseases. Acute graft v-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. The T lymphocytes were specially depleted by anti-CD5, CD2, CD8, CD27 monoclonal antibody-ricin immunotoxins. Inhibition of the protein synthesis and T-cell functions in the target cells was observed in vitro. At 10 9mol / L of the immunotoxin, 3 logs (99.9%) of target cells were killed, but no cytotoxicity on nontarget cells. At the same concentration, the anti T cell immunotoxin had no any influence on the proliferating rate of CFU-GM and BFU E. None of the ten patients who received T cell depleted bone marrow developed grade III or IV acute GVHD.

Objective: To investigate which step of IL-6 signal transduction pathways in myeloma cells can be taken as the acting target of the antagonists for IL-6. Methods: EMSA and immunoprecipitation were used to detect the activation of transcription factors(TFs)-STAT3, NF-IL-6 and protein kinase ERK in a myeloma cell line-Sko-007 by IL-6. then anti-sense expression plasmids and anti-sense ODN for these signal moleculars were constructed and designed,the effects of these anti-sense nucleic acids on IL-6 signal transduction in Sko-007 cells were analyzed by the same methods. Results: IL-6 signal transduction could be antagonized by these anti-sense nucleic acids at different extent.Conclusion: TFs or protein kinases in IL-6 signal trareduction pathways can be taken as the target for antagonists design.

Objective:To investigate the relation between the effects of IL 6 upon acute myeloid leukemia (AML) cells and its signal transduction mechanism Methods:Determined the effects of IL 6 on the growth of M1, R2, K562 and TF1 cells and the activation status of IL 6 induced nuclear factors (signal transducer and activator of transcription 3, STAT3 and nuclear factor IL6, NF IL6) by electrophoresis mobility shift assay (EMSA) Based upon these, blocked/reduced the activation of STAT3 or NF IL6 in M1 leukemia cells with STAT3/NF IL6 anti sense oligonucleotides (AS ODNs) and determined the oligonucleotides' effects upon IL 6 induced growth arrest of M1 cells Results:NF IL6 was constitutively activated in all these AML cells, while STAT3 was constitutively activated only in R2 and K562 cells Furthermore, STAT3 AS ODN reduced IL 6 induced growth arrest of M1 cells, while blocking/reducing of NF IL6 activation resulted in enhancing of IL 6 induced growth arrest Conclusion:JAK STATs pathway (especially STAT3) and Ras/MAPK pathway antagonize each other in proliferation regulation of AML cells

Objective:To study the inhibited function of CTLA4 Ig on T cell activation and its mechanism Methods:After separating fresh PBMC,the effects of CTLA4 Ig on T lymphocyte transformation and mixed lymphocyte reaction were analyzed,and its inhibitory effect on the CD25 expression on T cell surface was observed At last,the changes of the nuclear protein in active T cell were analyzed by the EMSA method.Results:CTLA4 Ig has an inhibitory effect on the lymphocyte transformation,MLR and CD25 expression on T cell surface,and it can inhibite the activation of RE/AP binding factor related to IL 2 expression. Conclusion:CTLA4 Ig inhibit the activation of T cell by multipathway,one of the mechanism might be its inhibitory effect on the activation of RE/AP binding factor.