Nanotech 2010

Novel internalizing immunoliposome targeting epithelioid and sarcomatoid subtypes of mesothelioma cancer cells

A.K. Iyer, X. Zhu, J. Feng, X. Lan, Y. Su, Y. Liu, C.V. Broaddus, H.F. VanBrocklin, B. Liu, J. He
University of California San Francisco, US

Keywords: antibody, scFv, immunoliposome, mesothelioma

Abstract:

Objective: Human antibodies targeting cancer cell surface epitopes may be useful for targeted imaging and therapy. We have recently identified a promising rapidly internalizing single chain antibody fragment (ScFv’s) (M1) that could selectively bind to mesothelioma derived from both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of tumor cells. The objective of this study is to evaluate the cell binding and internalization of an internalizing nanosize liposome, conjugated with rapid internalizing human single chain antibody fragment, to both subtypes of mesothelioma cells. Methods: Immunoliposome was synthesized by first forming liposome composed of POPC, cholesterol, mPEG-DSPE, and DMPE-DTPA in a 200:100:0.1:0.03 molar ratio, followed by insertion of M1 conjugated lipid (DSPE-PEG-M-40). 111In radiolabeling was achieved through DTPA chelator on the liposome. To determine the optimum number of ScFv/liposome that gave the best results on internalization of IL into mesothelioma cancer cells, varying number of ScFv/liposome was inserted onto 111In labeled liposome and incubated them with VAMT-1 cells at 37oC for 24h. At a fixed number of ScFv/liposome at 50, the effect of concentration of lipid (liposome) on the binding and internalization of 111In labeled IL in mesothelioma cells (VAMT-1 and M-28) was also investigated and compared it with a control cell line (BPH). Results: The internalization of the IL kept increasing as the number of ScFv/liposome increased until it reaches about 50-60 ScFv/liposome and above this number the internalization was independent on the number of ScFv/liposome (Fig.1A). At 24 h incubation (Fig. 1B), for both mesothelioma cells tested, the ratio of bound to internalized (% of total) was much higher (>85%) compared to the control cells (<40%), at all lipid concentrations studied, indicating the efficient and selective internalization of the M1-IL into mesothelioma cells of both epitheliod (M-28) and sarcomatoid (VAMT-1) origin. Conclusion: Liposome conjugated with rapid internalizing human single chain antibody fragment possesses the internalizing property to both subtypes of mesothelioma cells and potential for targeted drug delivery, imaging and therapy.
 
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