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LL2 is a murine monoclonal antibody (MAb) that has been shown to be effective for the diagnosis and treatment of patients with non-Hodgkin's B cell lymphoma. Studies have also shown that radiolabeled murine LL2 (mLL2) or mLL2 and fragments thereof coupled to Pseudomonas exotoxin (PE) can effectively target human B cell lymphoma in mice. We have obtained the DNA sequences encoding the VK and VH domains of mLL2, an IgG2a MAb, which were combined with their respective human kappa and IgG1 constant region domains and expressed in SP2/0 cells. Like its murine counterpart, the chimeric LL2 (cLL2) antibody is glycosylated in the light chain variable region. Chimerization did not interfere with the immunoreactivity of the antibody, as determined by a competitive binding assay, where either antibody shows equivalent inhibition of the binding of its counterpart to the Raji cell membrane surface antigen, CD22. Both antibodies bind and are rapidly internalized by Raji cells, whereas an irrelevant humanized antibody did not bind and was not internalized under similar conditions. The internalization rates of the bound murine or chimeric antibodies were nearly identical, with Ke values of 0.106 and 0.118 min-1 for mLL2 and cLL2, respectively. The observed close equivalence between the murine and chimeric antibodies suggests potential advantages of the latter as a less immunogenic agent. Studies are currently underway to evaluate the chimeric antibody as a potential therapeutic immunoconjugate.

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Abstract. Large amounts of cholestanol, the 5a-dihydro derivative of cholesterol are found in tissues of patients with the rare inherited sterol storage disease cerebrotendinous xanthomatosis. Although small amounts of cholestanol are present in virtually every tissue of normal man, little is known about its metabolism and effect on cholesterol and bile acid formation. The purpose of this study is to investigate the absorption and metabolism of cholestanol and its early effects on hepatic morphology and on the rate-limiting enzymes of cholesterol and bile acid biosynthesis. After 2 wk on a diet supplemented with 2% cholestanol, total liver sterol content increased by 48% (3.26 vs. 2.20 mg/g), and resulted in a significant rise in hepatic cholestanol concentration to 1.4 mg/g. However, cholestanol was less efficiently absorbed from the intestine than cholesterol and interfered with cholesterol absorption. Furthermore, hepatic hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity rose 2.6-fold (from 150.3 to 397.0 pmol/mg per min) during cholestanol feeding, and was associated with a marked proliferation of the smooth endoplasmic reticulum of the centrilobular areas. In addition, significant amounts of allocholic acid (16%) and allochenodeoxycholic acid (5%) were formed from cholestanol and excreted in the bile. These results show that cholestanol is absorbed from the intestine, interferes with cholesterol absorption, and is deposited in the liver. However, in contrast to cholesterol, cholestanol feeding was associated with a marked elevation of HMG-CoA

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