The Killing Effect Of Peripheral Blood T Lymphocytes Costimulated By Anti-CD3 And CD28 Combined With Gastrin Receptor Antagonist To Colon Cancer Cells

In the immmunotherapy of tumor, the adoptive immunity is a proposal of the tumor therapy in the past few years. It is a hot spot that the PBLs costimulated by McAb can treat the tumor.It was certificated by some experiments that the PBLs costimulated by CD28 and CD3 could kill the human liver carcinoma cells and bladder carcinoma cells. In addition, the gastrin is a frndamental gut hormone. It is secreted by the G cell. The G cell is a typical open type cell. It multitudinously resides in the sinus ventriculi, then resides in the fundus of gastricus,duodenum and jejunum. The gastrin can influence all the gastrointestinal tract. It can promote the externalization of the gastrointe stinal tract, increase the locomotion of the gastrointestinal unbrace the pyloric sphincter muscle and sphincter of Oddi and ileocecal and junction sphincter. It can promote the division growth of the cells of enteromucosa in the chylostomach and superior part intestinal tract, and promote the liberation of the insulinum and calcitionin. The gastrin not only possess the capability to excite the accrementition of entero- endepidermis, but also possess the important effect to accommodate the cell growth of the gastrointestinal tumor. The gastrin receptor antagonist possess the inhibitory action to the growth and metastasis of colon carcinoma.Aim:To investigate the killing effect of T cells costimulated by CD28 and CD3 McAb to the human colorectal carcinoma cell lines when combined with gastrin receptor antagonist.Methods:The cancer cells were cultured with T cells costimulated by anti-CD28 / CD3 McAb and/or CI-988. Then the growth curve of cells was obtained.The killing efficiency was measured by MTT method. The submicroscopic structure of cells was observed by electron microscope. Apoptosis was detected by a flow cytometer.Results:After treated with the costimulated T cells with anti-CD28 and CD3 for two days,the inhibition rate of HT-29 cells was 60.4%.When two reagents were used in combination,the inhibition rate was 89.5%. The killing effect of the combination of costimulated T cells by anti-CD28 and CD3 and CL-988 was superior in comparison to the single costimulated T cells therapy (P <0.01).Flow cytometer verified that cells apoptosized after exposed to costimulated T cells by anti-CD28 and CD80 (1mmol / L)and CI-988(1x10-mmol/L)12 h.The necrosis and apoptosis cells were observed in the electron microscope after the cancer cells were cultured with costimulated T cells and CI-988 for 72 h.Conclusions:Gastrin receptor antagonist can elevate the killing effect of Anti-CD28/ CD3stimulated cells on colorectal carcinoma.Apoptosis is possibly one of the reasons of the synergistic action.They perhaps kill carcinoma cells in two ways:necrosis and apoptosis.