Specific targeting of anti-CD59 siRNA by Herceptin®-conjugated liposomes improves complement-mediated cytotoxicity of breast carcinoma cells

Li, W.; Geis, Nicolas; Kirschfink, Michael

doi:10.1016/j.molimm.2009.05.222

Cited by 2 publications

(3 citation statements)

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“…Taken together, the results of our current study suggest that the simultaneous attack of HER2/neu-overexpressing USC with trastuzumab and with siRNA able to specifically target CD55 and CD59 in vivo might improve both CDC and trastuzumab ADCC against these biologically aggressive tumours. In this regard, although the lack of targeted siRNA delivery currently remains a major obstacle for its broad therapeutic in vivo application, recent evidence suggests that specific targeting of mCRP by nanoparticles and/or herceptin-conjugated liposomes is feasible and potentially able to improve antibody-based cancer immunotherapy ( Aigner, 2007 ; Li et al , 2007 , 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy

et al. 2012

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Background:We evaluated the expression of CD46, CD55 and CD59 membrane-bound complement-regulatory proteins (mCRPs) in primary uterine serous carcinoma (USC) and the ability of small interfering RNA (siRNA) against these mCRPs to sensitise USC to complement-dependent cytotoxicity (CDC) and antibody (trastuzumab)-dependent cellular cytotoxicity (ADCC) in vitro.Methods:Membrane-bound complement-regulatory proteins expression was evaluated using real-time PCR (RT–PCR) and flow cytometry, whereas Her2/neu expression and c-erbB2 gene amplification were assessed using immunohistochemistry, flow cytometry and fluorescent in-situ hybridisation. The biological effect of siRNA-mediated knockdown of mCRPs on HER2/neu-overexpressing USC cell lines was evaluated in CDC and ADCC 4-h chromium-release assays.Results:High expression of mCRPs was found in USC cell lines when compared with normal endometrial cells (P<0.05). RT–PCR and FACS analyses demonstrated that anti-mCRP siRNAs were effective in reducing CD46, CD55 and CD59 expression on USC (P<0.05). Baseline complement-dependent cytotoxicity (CDC) against USC cell lines was low (mean±s.e.m.=6.8±0.9%) but significantly increased upon CD55 and CD59 knockdown (11.6±0.8% and 10.7±0.9%, respectively, P<0.05). Importantly, in the absence of complement, both CD55 and CD59, but not CD46, knockdowns significantly augmented ADCC against USC overexpressing Her2/neu.Conclusion:Uterine serous carcinoma express high levels of the mCRPs CD46, CD55 and CD59. Small interfering RNA inhibition of CD55 and CD59, but not CD46, sensitises USC to both CDC and ADCC in vitro, and if specifically targeted to tumour cells, may significantly increase trastuzumab-mediated therapeutic effect in vivo.

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Section: Discussionmentioning

confidence: 99%

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy

et al. 2012

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“…Moreover, ligands with high affinity for formations located on the membrane of cancerous cells offer high selectivity towards these cells, potentially ameliorating the drugs' therapeutic index [51, 52]. However, there is room for improvement in both techniques.…”

Section: Physiochemistry Of Liposomesmentioning

confidence: 99%

“…As mentioned before, steric stabilization of liposomes is an indispensable method for achieving longer circulation times and giving the carrier the opportunity to extravasate to the tumoral site. Moreover, ligands with high affinity for formations located on the membrane of cancerous cells offer high selectivity towards these cells, potentially ameliorating the drugs' therapeutic index [ 51 , 52 ]. However, there is room for improvement in both techniques.…”

Section: Physiochemistry Of Liposomesmentioning

confidence: 99%

Optimizing Druggability through Liposomal Formulations: New Approaches to an Old Concept

et al. 2012

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Developing innovative delivery strategies remains an ongoing task to improve both efficacy and safety of drug-based therapy. Nanomedicine is now a promising field of investigation, rising high expectancies for treating various diseases such as malignancies. Putting drugs into liposome is an old story that started in the late 1960s. Because of the near-total biocompatibility of their lipidic bilayer, liposomes are less concerned with the safety issue related to the possible long-term accumulation in the body of most nanoobjects currently developed in nanomedicine. Additionally, novel techniques and recent efforts to achieve better stability (e.g., through sheddable coating), combined with a higher selectivity towards target cells (e.g., by anchoring monoclonal antibodies or incorporating phage fusion protein), make new liposomal drugs an attractive and challenging opportunity to improve clinical outcome in a variety of disease. This review covers the physicochemistry of liposomes and the recent technical improvements in the preparation of liposome-encapsulated drugs in regard to the scientific and medical stakes.

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Specific targeting of anti-CD59 siRNA by Herceptin®-conjugated liposomes improves complement-mediated cytotoxicity of breast carcinoma cells

Cited by 2 publications

References 0 publications

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy

Optimizing Druggability through Liposomal Formulations: New Approaches to an Old Concept

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