Antibody-Targeted Liposome

Straubinger, R. M., Lopez, N. G., Debs, R. J., Hong, K., and Papahadjopoulos, D. (1988). Liposome-based therapy of human ovarian cancer Parameters determining potency of negatively charged and antibody-targeted liposomes, Cancer Res.. 48, 5237-5245. 

Heath, T.D., Montgomery, J.A., Piper, J.R., and Papahadjopoulos, D. (1983) Antibody-targeted liposomes Increase in specific toxicity of methotrexate-g-aspartate. Proc. Natl Acad. Sci. USA 80, 1377-1381. 

Figure 1.1. Schematic representation of four major liposome types. Conventional liposomes are either neutral or negatively charged. Stealth liposomes are sterically stabilized and carry a polymer coating to obtain a prolonged circulation time in the body. Immunoliposomes are antibody targeted liposomes and can consist of either conventional or sterically stabilized liposomes. Positive charge on cationic liposomes can be created in various ways. Reproduced from reference [112] with permission.

Sapra P, Allen TM (2002) Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res 62 7190-7194... 

Renneisen, K., Leserman, L., Matthes, E Schroder, H. C., and Muller, W. E. (1990) Inhibition of expression of human immunodeficiency virus-1 in vitro by antibody-targeted liposomes containing antisense RNA to the env region../. Biol. Chem. 265, 16,337-16,342. 

Agrawal, A, K., Singhal, A., and Gupta, C, M. (1987). Functional targeting to erythrocytes in vivo using antibody bearing liposomes as drug vehicles, Biochem. Biophys. Res. Commun., 148, 357-361. 

Target-Sensitive Liposomes. For targeting liposomes to a specific site, antibody-coated liposomes or ligand-coated liposomes are usually used. Target-sensitive liposomes composed of PE and palmitoyl-antibody have been developed these are destabilized on binding to the target and release the contents at the specific site (46)... 

Fig. 13 Diagrammatic representation of two types of antibody-targeted systems. Drug is either covalently linked directly to the antibody or is contained in liposomes that are targeted by attached antibodies.

Covalent attachment of antibody molecules to liposomes can provide a targeting capacity to the vesicle that can modulate its binding to specific antigenic determinants on cells or to molecules in solution. Antibody-bearing liposomes may possess encapsulated components that can be used for detection or therapy (Figure 22.17). For instance, fluorescent molecules encapsulated within antibody-targeted vesicles can be used as imaging tools or in flow cytometry... 

Marty C, et al. Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scEv antibody modified liposomes. Br J Cancer 2002 87 106. 

Of the non-antibody, non-liposome based drug targeting strategies, most of the (limited) clinical experience has been obtained with polymer-based conjugates of anticancer drugs. The most widely employed drugs for this application are cytotoxic agents such as doxorubicin and... 

Houck, K.S. Huang, L. The role of multivalency in antibody mediated liposome targeting. Biochem. Biophys. Res. Commun. 1987, 145, 1205-1210. 

Matzku, S. Krempel, H. Weckenmann, H.P. Schirrma-cher, V. Sinn, H. Strieker, H. Tumour targeting with antibody-coupled liposomes failure to achieve accumulation in xenografts and spontaneous liver metastases. Cancer Immunol. Immunother. 1990, 31, 285-291. 

Marty, C. Odermatt, C.M. Schott, H. Neri, D. Ballmer-Hofer, K. Klemenz, R. Schwendener, R.A. Cytotoxic targeting of F9 teratocarcinoma tumors with anti-ED-B fibronectin scFv antibody modified liposomes. British Journal of Cancer 2002, 87, 106-112. 

When foreign cells enter the human body they are captured by antibodies, which attach themselves to the cell membrane surface. Complement binds to these antibodies in a specific order, after which the target cells are lysed. Because the liposome bilayer is structurally similar to the cell wall, complement can be used to completely lyse antibody-bound liposomes. Attention has to be paid to the fact that although complement is specific, some liposomes are susceptible to complement lysis, without being bound to an antibody. Most liposome immunoassays are homogeneous complement-based assays. 

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