Enzyme-linked immunosorbent assays for quantification of MMMAE-conjugated ADCs and total antibodies in cynomolgus monkey sera / 药物分析学报

Antibody-drug conjugates(ADCs)are commonly heterogeneous and require extensive assessment of exposure-efficacy and exposure-safety relationships in preclinical and clinical studies.In this study,we report the generation of a monoclonal antibody against monomethyl auristatin E(MMAE)and the development,validation,and application of sensitive and high-throughput enzyme-linked immunosor-bent assays(ELISA)to measure the concentrations of MMAE-conjugated ADCs and total antibodies(tAb,antibodies in ADC plus unconjugated antibodies)in cynomolgus monkey sera.These assays were suc-cessfully applied to in vitro plasma stability and pharmacokinetic(PK)studies of SMADC001,an MMAE-conjugated ADC against trophoblast cell surface antigen 2(TROP-2).The plasma stability of SMADC001 was better than that of similar ADCs coupled with PEG4-Val-Cit,Lys(m-dPEG24)-Cit,and Val-Cit linkers.The developed ELISA methods for the calibration standards of ADC and tAb revealed a correlation be-tween serum concentrations and the OD450 values,with R2 at 1.000,and the dynamic range was 0.3-35.0 ng/mL and 0.2-22.0 ng/mL,respectively;the intra-and inter-assay accuracy bias％ranged from-12.2％to-5.2％,precision ranged from-12.4％to-1.4％,and the relative standard deviation(RSD)was less than 6.6％and 8.7％,respectively.The total error was less than 20.4％.The development and validation steps of these two assays met the acceptance criteria for all addressed validation parameters,which suggested that these can be applied to quantify MMAE-conjugated ADCs,as well as in PK studies.Furthermore,these assays can be easily adopted for development of other similar immunoassays.

A case of neurofibromatosis complicated with small bowel obstruction / 浙江大学学报·医学版

Neurofibromatosis type 1(NF-1) with gastrointestinal stromal tumor (GIST) is a rare case in clinical practice. But it is even rarer that the GIST tumor in this case is so large that it cause small intestinal obstruction. Here we report such a male case of NF-1,with positive family history of NF-1 and nodules all over the patient's skin and abdominal cavity. The patient came to hospital with a sudden upper abdominal pain and nausea and vomiting over 5 d. Abdominal computerized tomography (CT) showed that there were numerous nodules of different size in his abdominal cavity. And the largest one is about 10 cm in diameter,which oppressed the small bowel and caused the small bowel mesenteric volvulus and obstruction of the bowel. Finally,the tumor was pathologically proved to be a GIST tumor but not NF nodule. The patient stays healthy until now after operation.