Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into B...Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into BALB/c(H- 2d) mice. This model was used to investigate the possibility of immunosuppressive induction with CD44 McAb, leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1). Results: Treatment of the allograft recipients with CD44 McAb alone, or both LFA-1 and ICAM-1 or combination of these 3 McAb significantly prolonged the cardiac allografts survival as compared with PBS controls (P<0.01). The combination of anti-CD44 and ICAM-1 and LFA-1 McAb was shown to produce more significant prolongation of grafts survival than anti-CD44 McAb alone or both anti-ICAM- 1 and LFA-1 McAb (P < 0.01). Histological examination of the grafts treated with the McAb displayed greatly reduced mononuclear cell infiltration. The proliferation of spleen cells from recipient BALB/c with McAb treatment was significantly inhibited in response to the stimulators of C57BL/6 spleen cells, but increased upon the stimulation of C3H/He (H-2k) spleen cells, as demonstrated by mixed lymphocyte reaction. Similarly, the cytotoxic activity against donor H-2-compatible (H-2b) target cells, EL-4 cells, was significantly suppressed. The spleen cells from allografted recipient BALB/c mice with McAb treatment induced specific tolerance for C57BL/6 cardiac grafts in allografted recipients, whereas those from allografted BALB/c mice without McAb treatment induced acute rejection. Conclusion: These results indicate that antiadhesion therapy using a combination of McAb to adhesion molecules can induce specific immunosuppression of transplant rejection.展开更多
Advanced gastric cancer is a common digestive system tumor,and its treatment has always been a difficult problem.In recent years,with the rapid development of immunotherapy,the treatment effect of advanced gastric can...Advanced gastric cancer is a common digestive system tumor,and its treatment has always been a difficult problem.In recent years,with the rapid development of immunotherapy,the treatment effect of advanced gastric cancer has been significantly improved.This article introduces the current status and clinical research progress of immune checkpoint inhibitors in advanced gastric cancer.Commonly used immunotherapy methods include chemical drug therapy,biological therapy,and gene therapy,among which the immune checkpoint inhibitors are currently one of the most popular immunotherapy methods,including nivolumab,pembrolizumab,and atezolizumab,which target programmed death ligand 1(PD-L1)low expression(1%–49%)and PD-L1 high expression(≥50%).The results of clinical studies have shown that immunotherapy can significantly prolong the survival of patients with advanced gastric cancer while having lower toxic side effects and better tolerance.However,immunotherapy also has some problems,such as drug resistance and repeated infection.Future research directions include exploring new immunotherapy methods,combination therapy,and individualized therapy.展开更多
文摘Objective:To evaluate the immunosuppressive effect of monoclonal antibodies (McAb) against cell surface adhesion molecules on transplant rejection. Methods: C57BL/6 (H-2b) mouse cardiac grafts were transplanted into BALB/c(H- 2d) mice. This model was used to investigate the possibility of immunosuppressive induction with CD44 McAb, leukocyte function associated antigen (LFA-1) and intercellular adhesion molecule (ICAM-1). Results: Treatment of the allograft recipients with CD44 McAb alone, or both LFA-1 and ICAM-1 or combination of these 3 McAb significantly prolonged the cardiac allografts survival as compared with PBS controls (P<0.01). The combination of anti-CD44 and ICAM-1 and LFA-1 McAb was shown to produce more significant prolongation of grafts survival than anti-CD44 McAb alone or both anti-ICAM- 1 and LFA-1 McAb (P < 0.01). Histological examination of the grafts treated with the McAb displayed greatly reduced mononuclear cell infiltration. The proliferation of spleen cells from recipient BALB/c with McAb treatment was significantly inhibited in response to the stimulators of C57BL/6 spleen cells, but increased upon the stimulation of C3H/He (H-2k) spleen cells, as demonstrated by mixed lymphocyte reaction. Similarly, the cytotoxic activity against donor H-2-compatible (H-2b) target cells, EL-4 cells, was significantly suppressed. The spleen cells from allografted recipient BALB/c mice with McAb treatment induced specific tolerance for C57BL/6 cardiac grafts in allografted recipients, whereas those from allografted BALB/c mice without McAb treatment induced acute rejection. Conclusion: These results indicate that antiadhesion therapy using a combination of McAb to adhesion molecules can induce specific immunosuppression of transplant rejection.
基金supported by grants from The National Natural Science Foundation of China(Y4JM061001,Y5JY011001,81072093)The Natural Science Foundation of Hebei Province(C2012401039)~~
文摘Advanced gastric cancer is a common digestive system tumor,and its treatment has always been a difficult problem.In recent years,with the rapid development of immunotherapy,the treatment effect of advanced gastric cancer has been significantly improved.This article introduces the current status and clinical research progress of immune checkpoint inhibitors in advanced gastric cancer.Commonly used immunotherapy methods include chemical drug therapy,biological therapy,and gene therapy,among which the immune checkpoint inhibitors are currently one of the most popular immunotherapy methods,including nivolumab,pembrolizumab,and atezolizumab,which target programmed death ligand 1(PD-L1)low expression(1%–49%)and PD-L1 high expression(≥50%).The results of clinical studies have shown that immunotherapy can significantly prolong the survival of patients with advanced gastric cancer while having lower toxic side effects and better tolerance.However,immunotherapy also has some problems,such as drug resistance and repeated infection.Future research directions include exploring new immunotherapy methods,combination therapy,and individualized therapy.
