Glycosylation patterns commonly change in cancer, resulting in expression of tumor-associated carbohydrate antigens (TACA). While promising, currently available anti-glycan antibodies are not useful for clinical cancer therapy. Here, we show that potent anti-glycan antibodies can be engineered to acquire cancer therapeutic efficacy. We designed yeast surface display to generate and select for therapeutic antibodies against the TACA SLea (CA19−9) in colon and pancreatic cancers. Elite clones showed increased affinity, better specificity, improved binding of human pancreatic and colon cancer cell lines, and increased complement-dependent therapeutic efficacy. Molecular modeling explained the structural basis for improved antibody functionality at the molecular level. These new tools of directed molecular evolution and selection for effective anti-glycan antibodies, provide insights into the mechanisms of cancer therapy targeting glycosylation, and provide major methodological advances that are likely to open up innovative avenues of research in the field of cancer theranostics.
Risk stratification in acute myocarditis is based on the clinical signs of heart failure, the degree of cardiac dysfunction, and the findings in cardiac magnetic resonance (CMR). The aim of the current study is to examine the prognostic yield of the natriuretic peptide N-terminal-pro hormone Brain Natriuretic Peptide (NT-proBNP) and C-reactive protein (CRP) in acute myocarditis among patients with preserved/mildly reduced left ventricular ejection fraction (LVEF). We retrospectively analyzed 59 patients (median age 28 years, 76% males) with ICD-9 discharge diagnosis of acute myocarditis. Basic characteristics, echocardiographic, and laboratory parameters were obtained from computerized files. The median length of stay was 3, (IQR 2–5) days, and the median LVEF was 48% (IQR, 54–62%). High levels of NT-proBNP and CRP were associated with increased length of stay (r = 0.57, p < 0.001; r = 0.4 p = 0.001, respectively), while troponin level was not (r = 0.068, p = 0.61). During the index hospitalization, complications occurred in 14 (23.7%) patients. High NT-proBNP and CRP levels were associated with complications (p < 0.001, and p = 0.001, respectively), while troponin level was not (p = 0.452). In conclusion, routine measurement of NT-proBNP and CRP are preferred over troponin for risk stratification in hemodynamically stable myocarditis.
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