Abstract：
:A great deal of interest has surrounded the activities of monoclonal antibodies (mAbs), and mAb-drug, toxin and radionuclide conjugates for the treatment of human cancers. In the last few years, a number of new mAb-based reagents have been clinically approved (Rituxan, Herceptin, and Panorex), and several others are now in advanced clinical trials. Successful therapeutic treatment of solid tumors with drug conjugates of such macromolecules must overcome the barriers to penetration within tumor masses, antigen heterogeneity, conjugated drug potency, and efficient drug release from the mAbs inside tumor cells. An alternative strategy for drug delivery involves a two-step approach to cancer therapy in which mAbs are used to localize enzymes to tumor cell surface antigens. Once the conjugate binds to the cancer cells and clears from the systemic circulation, antitumor prodrugs are administered that are catalytically converted to active drugs by the targeted enzyme. The drugs thus released are capable of penetrating within the tumor mass and eliminating both cells that have and have not bound the mAb-enzyme conjugate. Significant therapeutic effects have been obtained using a broad range of enzymes along with prodrugs that are derived from both approved anticancer drugs and highly potent experimental agents. This review focuses on the activities of several mAb-enzyme/prodrug combinations, with an emphasis on those that have provided mechanistic insight, clinical activity, novel protein constructs, and the potential for reduced immunogenicity.
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
Senter PD,Springer CJdoi
10.1016/s0169-409x(01)00206-xsubject
Has Abstractpub_date
2001-12-31 00:00:00pages
247-64issue
3eissn
0169-409Xissn
1872-8294pii
S0169-409X(01)00206-Xjournal_volume
53pub_type
杂志文章,评审abstract：:The novel corona virus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the globe at a formidable speed, causing tens of millions of cases and more than one million deaths in less than a year of its report in December 2019. Since then, companies and research institutions have r...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2020.12.008
更新日期：2021-02-01 00:00:00
abstract：:The effective delivery of antigens via the oral route is an extremely desirable goal. Mucosal delivery of antigens stimulates mucosal and systemic immunity without affecting maternal antibodies and reduces the need for sterile needles or trained personnel. To date, there are very few commercially available oral vaccin...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2004.09.009
更新日期：2005-01-10 00:00:00
abstract：:Novel drug delivery systems based on microtechnology have advanced tremendously, but yet face some technological and societal hurdles to fully achieve their potential. The novel drug delivery systems aim to deliver drugs in a spatiotemporal- and dosage-controlled manner with a goal to address the unmet medical needs f...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2017.11.003
更新日期：2018-03-15 00:00:00
abstract：:Modern pharmaceutical delivery systems are intended to produce plasma drug concentration versus time profiles that result in optimum therapeutic efficacy and a minimum of drug concentration-dependent adverse effects. To accomplish this requires that the drug delivery rate and temporal profile be based on the pharmacok...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(98)00028-3
更新日期：1998-09-07 00:00:00
abstract：:An oral form of insulin has been the elusive goal for many investigators since the protein's initial discovery by Banting and Best in 1922. This paper will attempt to answer why this is the case by describing the substantial barriers to the development of oral insulin formulations. Following this description, specific...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(98)00075-1
更新日期：1999-02-01 00:00:00
abstract：:Poly(lactic acid) (PLA) is a synthetic polyester that has shown extensive utility in tissue engineering. Synthesized either by ring opening polymerization or polycondensation, PLA hydrolytically degrades into lactic acid, a metabolic byproduct, making it suitable for medical applications. Specifically, PLA nanofibers ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.04.019
更新日期：2016-12-15 00:00:00
abstract：:The supramolecular structures formed between cyclodextrins (CDs) and polymers have inspired interesting developments of novel supramolecular biomaterials. This review will update the recent progress in studies on supramolecular structures based on CDs and block copolymers, followed by the design and synthesis of CD-ba...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2008.02.011
更新日期：2008-06-10 00:00:00
abstract：:Recent pre-clinical and clinical studies have shown that stem cell-based therapies hold tremendous promise for the treatment of human disease. Mesenchymal stem cells (MSC) are emerging as promising anti-cancer agents which have an enormous potential to be utilized to treat a number of different cancer types. MSC have ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.06.010
更新日期：2012-06-01 00:00:00
abstract：:Nanotechnology has the potential to open many novel diagnostic and treatment avenues for disorders of the central nervous system (CNS). In this review, we discuss recent developments in the applications of nanotechnology in CNS therapies, diagnosis and biology. Novel approaches for the diagnosis and treatment of neuro...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2019.02.009
更新日期：2019-08-01 00:00:00
abstract：:The great interest in mucosal vaccine delivery arises from the fact that mucosal surfaces represent the major site of entry for many pathogens. Among other mucosal sites, nasal delivery is especially attractive for immunization, as the nasal epithelium is characterized by relatively high permeability, low enzymatic ac...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2008.09.005
更新日期：2009-02-27 00:00:00
abstract：:Transcriptional targeting using a mammalian cellular promoter to restrict transgene expression to target cells is often desirable for gene therapy. This strategy is, however, hindered by relatively weak activity of some cellular promoters, which may lead to low levels of gene expression, thus declining therapeutic eff...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2009.02.007
更新日期：2009-07-02 00:00:00
abstract：:Oral lipid-based drug delivery systems may include a broad range of oils, surfactants, and cosolvents. This diversity makes comparison of lipid-based formulations difficult. Although the relationship between formulation and drug absorption is understood at a conceptual level, performance in vivo cannot be predicted wi...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2007.10.010
更新日期：2008-03-17 00:00:00
abstract：:The assessment of percutaneous permeation of molecules is one of the main steps in the initial design and later in the evaluation of dermal or transdermal drug delivery systems. The literature reports numerous ex vivo, in vitro and in vivo models used to determine drug skin permeation profiles and kinetic parameters, ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2007.07.004
更新日期：2007-09-30 00:00:00
abstract：:Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ERα and ERβ, which mediate proliferation and differentiation of cells. For decades, ERα mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most notably with the selective estrogen r...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2010.08.001
更新日期：2010-10-30 00:00:00
abstract：:Synthetic micro/nanomotors are tiny devices than can be self-propelled or externally powered in the liquid phase by different types of energy source including but not limited to: catalytic, magnetic or acoustic. Showing a myriad of mechanical movements, building block materials, sizes, shapes and propulsion mechanisms...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2015.09.004
更新日期：2015-12-01 00:00:00
abstract：:DNA plasmid-based gene expression systems are being widely investigated for the potential treatment of genetic and acquired disease and for DNA-based vaccination. A number of human clinical trials are in progress using plasmid-based drugs. The regulatory framework that has been applied to biologicals such as recombina...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(97)00105-1
更新日期：1998-03-02 00:00:00
abstract：:Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting 'the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(00)00129-0
更新日期：2001-03-01 00:00:00
abstract：:Carbon-based functional nanomaterials have attracted immense scientific interest from many disciplines and, due to their extraordinary properties, have offered tremendous potential in a diverse range of applications. Among the different carbon nanomaterials, graphene is one of the newest and is considered the most imp...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.08.009
更新日期：2016-10-01 00:00:00
abstract：:The composition and architecture of the stratum corneum render it a formidable barrier to the topical and transdermal administration of therapeutic agents. The physicochemical constraints severely limit the number of molecules that can be considered as realistic candidates for transdermal delivery. Iontophoresis provi...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2003.10.026
更新日期：2004-03-27 00:00:00
abstract：:The future of non-viral gene therapy depends on a detailed understanding of the barriers to delivery of polynucleotides. These include physicomechanical barriers, which limit the design of delivery devices, physicochemical barriers that influence self-assembly of colloidal particulate formulations, and biological barr...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(00)00133-2
更新日期：2001-03-01 00:00:00
abstract：:A recombinant C-terminal truncated form of the human soluble tumor necrosis factor receptor type I (sTNF-RI) was produced in E. coli. This soluble receptor contains the first 2.6 of the 4 domains of the intact sTNF-RI molecule. A monoPEGylated form of this molecule was produced using a 30 kD methoxyPEG aldehyde with a...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/s0169-409x(03)00112-1
更新日期：2003-09-26 00:00:00
abstract：:The development of lipid-based delivery vehicles for therapeutic molecules has become a topic of intense research. Recently, much of this effort has been directed towards mimicking the characteristics of viruses that give them an advantage for the delivery of genetic medicines. One of the most desirable properties of ...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章
doi：10.1016/s0169-409x(99)00032-0
更新日期：1999-08-20 00:00:00
abstract：:Antibodies can have exquisite specificity of target recognition and thus generate highly selective outcomes following their systemic administration. While antibodies can have high specificity, the doses required to treat patients, particularly for a chronic condition, are typically large. Fortunately, advances in prod...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2006.03.011
更新日期：2006-08-07 00:00:00
abstract：:Toxicity of nanocarrier systems involves physiological, physicochemical, and molecular considerations. Nanoparticle exposures through the skin, the respiratory tract, the gastrointestinal tract and the lymphatics have been described. Nanocarrier systems may induce cytotoxicity and/or genotoxicity, whereas their antige...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2007.11.007
更新日期：2008-05-22 00:00:00
abstract：:Small interfering RNA (siRNA) has a huge potential for the treatment or prevention of various lung diseases. Once the RNA molecules have successfully entered the target cells, they could inhibit the expression of specific gene sequence through RNA interference (RNAi) mechanism and generate therapeutic effects. The big...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.02.006
更新日期：2012-01-01 00:00:00
abstract：:Endosomes and lysosomes play a critical role in various aspects of cell physiology such as nutrient sensing, receptor recycling, protein/lipid catabolism, and cell death. In drug delivery, endosomal release of therapeutic payloads from nanocarriers is also important in achieving efficient delivery of drugs to reach th...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.08.014
更新日期：2017-04-01 00:00:00
abstract：:The bloodstream is the main transporting pathway for drug delivery systems (DDS) from the site of administration to the intended site of action. In many cases, components of the vascular system represent therapeutic targets. Endothelial cells, which line the luminal surface of the vasculature, play a tripartite role o...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2020.06.013
更新日期：2020-01-01 00:00:00
abstract：:Angiogenesis is naturally balanced by many pro- and anti-angiogenic factors while an imbalance of these factors leads to aberrant angiogenesis, which is closely associated with many diseases. Gene therapy has become a promising strategy for the treatment of such a disordered state through the introduction of exogenous...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2016.11.003
更新日期：2017-09-15 00:00:00
abstract：:Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for neural regeneration and niche modification in physiopathological conditions, harnessing the capability to modify from neuronal circuits to glial scar. Findings exposing the vast plasticity and potential of NSPCs have accumulated over the pas...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2017.07.016
更新日期：2017-10-01 00:00:00
abstract：:Computational Fluid Dynamics (CFD) and Discrete Element Modelling (DEM) studies relevant to inhaled drug delivery are reviewed. CFD is widely used in device design to determine airflow patterns and turbulence levels. CFD is also used to simulate particles and droplets, which are subjected to various forces, turbulence...
journal_title：Advanced drug delivery reviews
pub_type： 杂志文章,评审
doi：10.1016/j.addr.2011.10.004
更新日期：2012-03-30 00:00:00
