The use of single chain Fv as targeting agents for immunoliposomes: an update on immunoliposomal drugs for cancer treatment

Abstract

Importance of the field-Targeted liposomal drugs represent the next evolution of liposomal drug delivery in cancer treatment. In various preclinical cancer models, antibody-targeted PEGylated liposomal drugs have demonstrated superior therapeutic effects over their non-targeted counterparts. Single chain Fv (scFv) has gained popularity in recent years as the targeting agent of choice over traditional targeting agents such as monoclonal antibodies (mAb) and antibody fragments (e.g., Fab′).Areas covered in this review-This review is focused mainly on advances in scFv-targeted liposomal drug delivery for the treatment of cancers, based on a survey of the recent literature, and on experiments done in a murine model of human B-lymphoma, using anti-CD19 targeted liposomes targeted with whole mAb, Fab′ fragments and scFv fragments.What the reader will gain-This review examines the recent advances in PEGylated immunoliposomal drug delivery, focusing on scFv fragments as targeting agents, in comparison with Fab′ and mAb.Take home message-For clinical development, scFv are potentially preferred targeting agents for PEGylated liposomes over mAb and Fab′, owing to factors such as decreased immunogenicity, and pharmacokinetics/biodistribution profiles that are similar to non-targeted PEGylated (Stealth ® ) liposomes.

Poly aspartic acid peptide-linked PLGA based nanoscale particles: Potential for bone-targeting drug delivery applications

“…These include large molecular size, high production cost, and unwanted immune response (Lu et al, 2013). In addition, antibody-based drug delivery may result in nonspecific antibody uptake by Fc receptor-expressing normal cells, which will cause higher toxicity in bone marrow and liver (Cheng and Allen, 2010). These limitations can be overcome by using a short peptide sequence, which is smaller in molecular size, less immunogenic, inexpensive to produce, and easy to manipulate (Lu et al, 2013;Lee et al, 2007).…”

Subtype-specific binding peptides enhance the therapeutic efficacy of nanomedicine in the treatment of ovarian cancer

“…Although monoclonal antibodies (mAbs) and other large protein ligands have been used as therapeutics in the clinic and studied for targeted delivery [26][27][28], their potential for use as a drug delivery system has been limited due to a number of factors, including large molecular size, poor penetration into tumor tissues, and high immunogenicity when used in immunoliposomes. Furthermore, antibody-conjugated drug delivery may lead to higher than normal levels of toxicity in the liver and bone marrow due to nonspecific antibody uptake by Fc receptorexpressing normal cells [29]. These limitations can be overcome by using peptide ligands, which are smaller, less immunogenic, and more cost-effective to produce and manipulate [15].…”

Immune responses of therapeutic lipid nanoparticles

“…This technology has been widely used for targeted delivery of drugs [50] . However, the immunogenicity of immunoliposomes has been the major issue of this technology.…”

“…This immune response could cause severe hypersensitivity reactions in animals. Employment of humanized antibody or small fragments of antibody such as Fab (fragment, antigen binding region) and single chain fragment variable (scFv) has been suggested to reduce immunogenicity of the resulting immunoliposomes [50] .…”