RESUMEN
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer but has shown limited success to date in the treatment of advanced stage. Recruitment of T cells for cancer treatment is a rapidly growing strategy in immunotherapy such as chimeric antigen receptor T cells and bispecific antibodies. However, unwanted aggregations, structural instability or short serum half-life are major challenges of bispecific antibodies. Here, we developed a new format of T cell-redirecting antibody that is bispecific for membrane proteoglycans GPC3 of HCC and the T-cell-specific antigen CD3, which demonstrated to be favorable stability and productivity. Cross-linking of T cells with GPC3 positive tumor cells by the anti-GPC3/CD3 bispecific antibody-mediated potent GPC3-dependent and concentration-dependent cytotoxicity in vitro. Administration of the bispecific antibody with different concentrations in murine xenograft models of human HCC significantly inhibited tumor growth. In addition, no effects on tumor growth were observed in the absence of human effector cells or the bispecific antibody. Taken together, the anti-GPC3/CD3 bispecific antibody might be a potential therapeutic treatment for HCC.
Asunto(s)
Anticuerpos Biespecíficos/metabolismo , Carcinoma Hepatocelular/genética , Glipicanos/uso terapéutico , Inmunoterapia/métodos , Neoplasias Hepáticas/genética , Animales , Carcinoma Hepatocelular/patología , Femenino , Glipicanos/farmacología , Humanos , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos NODRESUMEN
OBJECTIVE: To establish a magnetic particle antibody immunoassay (MPAIA) for the detection of specific antibody in sera of schistosomiasis patients. METHODS: Fluorescein isothiocyanate (FITC) was used to label Schistosoma japonicum soluble egg antigen (Sj-SEA). Anti-human IgG coated with alkaline phosphatase (ALP) as enzyme-labeled second antibody, and magnetic beads were coupled with sheep anti-FITC antibody as solid phase. Phenolphthale in monophosphate was used as substrate to set up MPAIA for the detection. Serum samples from cases with schistosomiasis or other helminth infections were tested. RESULTS: The positive rate of MPAIA was 96.7% (116/120) with the sera of S. japonicum-infected cases. No cross reaction was observed with sera of trichinellosis, paragonimiasis or cysticercosis cases. The positive titer with reference sample was 1: 1,600. The precision was lower than 10%. The MPAIA tips can be stored at 4 degrees C for 12 months. CONCLUSION: MPAIA shows a high sensitivity, proper specificity and long-term validity for schistosomiasis detection.