Human CD33 ELISA Matched Antibody Pair

Gastric cancer (GC) is the most common malignant tumor in digestive organs, and the prognosis of GC patients who have undergone surgery remains poor because of frequent recurrence. Therefore, the identification of new markers to predict the outcome of these patients is needed. Monocyte count is a negative prognostic factor associated with inflammation. We investigated the relationship between peripheral monocytes in the peri-operative period and prognosis in GC patients. A high pre-operative monocyte count was identified as a prognostic factor in a retrospective analysis of 278 stage II and III GC patients who underwent curative gastrectomy. In contrast, an increased post-operative monocyte count compared to the pre-operative monocyte count was a marker of poor prognosis, particularly for early relapse. In a prospective analysis of 75 GC patients, a subset of the increased post-operative monocytes was similar to CD14(+) HLA-DR- CD11b(+) CD33(+) cells by flow cytometry, and these monocytes produced IDO and arginase and suppressed T cell functions; therefore, we classified these cells as monocytic myeloid-derived suppressive cells (M-MDSCs). Peri-operative neutrophils and C-reactive protein (CRP), which are also related to inflammation, did not affect the prognosis of GC patients, and a neutrophil immunosuppressive function was not observed. These results suggest that peripheral monocytes in the peri-operative period in GC patients are a useful marker for the prognosis of GC patients, and a subset of increased post-operative monocytes may be characterized as M-MDSCs.

Gemtuzumab ozogamicin (GO), an anti-CD33 antibody linked to calicheamicin via an acid-labile linker, is the first antibody-drug conjugate (ADC). The acidic environment inside lysosomes of target cells is an important intracellular determinant of the cytocidal action of GO, as the linker is hydrolyzed under acidic conditions. However, lysosomal activity in acute myeloid leukemia (AML) blasts in GO therapy has been insufficiently evaluated. It has been suggested that lysosome activity is suppressed in AML due to hyperactivation of the phosphoinositide 3-kinase/Akt pathway. We therefore hypothesized that agents which activate lysosomal function would potentiate the cytotoxicity of GO. Here, we found that a clinically useful mTORC1/2 dual inhibitor, AZD2014, reduced pH in the acidic organelles, including lysosomes, as shown by increased LysoTracker fluorescent intensity, and synergistically enhanced the cytotoxic effect of GO in primary leukemia cells. GO-induced cytotoxicity appeared to be enhanced with the increase in lysosomal activity by AZD2014. These results indicate that AZD2014 activated lysosomal function in primary leukemia cells, which in turn enhanced the cytotoxicity of GO. Enhancement of lysosomal activity may represent a new therapeutic strategy in the treatment of GO and other ADCs, particularly in cases with low lysosomal activity.