Abstract:
:Immunotherapy is a powerful anti-cancer treatment modality. However, despite numerous encouraging results obtained in pre-clinical studies, a definite breakthrough towards an established clinical treatment modality has as yet not occurred. Antibodies against tumor antigens have been shown to localise at the site of the tumor, but inadequate triggering of immune effector mechanisms have thwarted clinical efficacy thus far. Cellular immunotherapy has been hampered by limitations such as lack of specificity, down-regulation of major histocompatibility complex (MHC)-expression or Fas ligand up-regulation on tumor cells. This review focuses on the use of bispecific antibodies (BsAbs) for immunotherapy of cancer. Using BsAbs, it is possible to take advantage of the highly specific binding characteristics of antibodies and combine these with the powerful effector functions of cytotoxic immune effector cells. BsAbs share two different, monoclonal antibody-derived, antigen-recognizing moieties within one molecule. By dual binding, BsAbs reactive with a trigger molecule on an immune effector cell on the one hand and a surface antigen on a tumor target cell on the other are thus able to functionally focus the lytic activity of the immune effector cell towards the target cell. Over the last few years, the concept of BsAb-mediated tumor cell killing has been studied extensively both in preclinical models and in a number of phase I clinical trials. Promising pre-clinical results have been reported using tumor models in which diverse immune effector cell populations have been used. Despite this pre-clinical in vivo efficacy, the first clinical trials indicate that we are still not in a position to successfully treat human malignancies. This review discusses the production of BsAbs, the choice of trigger molecules in combination with potential effector cells and the preclinical models that have led to the current use of BsAbs in experimental clinical trials. It has become clear that appropriate immune cell activation and establishing a favourable effector-to-target cell ratio will have direct impact on the efficacy of the therapeutic approaches using BsAbs. New directions are discussed, i.e. finding appropriate dosage schemes by which immune effector cells become redirected without inducing hyporesponsiveness, defining possibilities for combining different immune effector cell populations and creating an in situ tumor environment that allows maximal tumoricidal activity
journal_name
Adv Drug Deliv Revjournal_title
Advanced drug delivery reviewsauthors
de Leij L,Molema G,Helfrich W,Kroesen BJdoi
10.1016/s0169-409x(97)00096-3subject
Has Abstractpub_date
1998-04-06 00:00:00pages
105-129issue
1-2eissn
0169-409Xissn
1872-8294pii
S0169409X97000963journal_volume
31pub_type
杂志文章abstract::Nucleic acids have gained a lot of interest for the treatment of ocular diseases. The first to enter in clinic has been Vitravene an antisense oligonucleotide for the treatment of cytomegalovirus (CMV) infection and more recently, research on aptamers have led to the marketing of anti-vascular endothelial growth facto...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.07.020
更新日期:2006-11-15 00:00:00
abstract::Hydrogels are synthetic or natural polymer networks that closely mimic native extracellular matrices. As hydrogel-based vehicles are being increasingly employed in therapeutic cell delivery, two inherent traits of most common hydrogels, namely low cell affinity and high cell constraint, have significantly drawn the at...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.02.001
更新日期:2010-06-15 00:00:00
abstract::Lipid-coated microbubbles represent a new class of agents with both diagnostic and therapeutic applications. Microbubbles have low density. Stabilization of microbubbles by lipid coatings creates low-density particles with unusual properties for diagnostic imaging and drug delivery. Perfluorocarbon (PFC) gases entrapp...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2003.12.006
更新日期:2004-05-07 00:00:00
abstract::One of the most common causes of illnesses in humans is from respiratory tract infections caused by bacterial, viral or fungal pathogens. Inhaled anti-infective drugs are crucial for the prophylaxis and treatment of respiratory tract infections. The benefit of anti-infective drug delivery via inhalation is that it aff...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.11.004
更新日期:2015-05-01 00:00:00
abstract::Cancer treatment regimens often include multiple anticancer agents targeting different cellular mechanisms in delicate balance with associated toxicity. Drug delivery systems offer a unique tool in the treatment of cancer, and applications in the local treatment of cancer have demonstrated utility in providing sustain...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2009.04.010
更新日期:2009-08-10 00:00:00
abstract::Quantitative structure-activity relationships have long been considered a vital component of drug discovery and development, providing insight into the role of molecular properties in the biological activity of similar and unrelated compounds. Recognition that in vitro bioassay and/or pre-clinical activity are insuffi...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.08.002
更新日期:2006-11-30 00:00:00
abstract::High affinity antibodies are crucial both for the discovery and validation of biomarkers for human health and disease and as clinical diagnostic and therapeutic reagents. This review describes some of the latest technologies for the design, mutation and selection of high affinity antibodies that provide a paradigm for...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2006.01.025
更新日期:2006-08-07 00:00:00
abstract::Cyclodextrins are useful functional excipients that have enjoyed widespread attention and use. The basis for this popularity from a pharmaceutical standpoint, is the ability of these materials to interact with poorly water-soluble drugs and drug candidates resulting in an increase in their apparent water solubility. T...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.05.012
更新日期:2007-07-30 00:00:00
abstract::Transdermal and rectal routes of drugs are very important as a useful supplement of oral routes and the direct exposing method of drugs when the systemic and local effects are required. The widespread use of parent cyclodextrins (CDs) and chemically modified CD derivatives (CD derivatives) for in-vitro and in-vivo der...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(98)00056-8
更新日期:1999-03-01 00:00:00
abstract::Cell surface receptors play a central role in the regulation of both cellular and systemic physiology by mediating intercellular communication, facilitating protein trafficking, and regulating virtually all intracellular processes. Receptor expression is often cell specific and is determined by cellular lineage, genet...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00079-3
更新日期:1998-02-02 00:00:00
abstract::A wide range of polymeric scaffolds have been intensively studied for use as implantable and temporal devices in tissue engineering. Biodegradable and biocompatible scaffolds having a highly open porous structure and good mechanical strength are needed to provide an optimal microenvironment for cell proliferation, mig...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.03.015
更新日期:2007-05-30 00:00:00
abstract::This review presents a summary of the various types of cellular therapy used to treat spinal cord injury. The inhibitory environment and loss of axonal connections after spinal cord injury pose many obstacles to regenerating the lost tissue. Cellular therapy provides a means of restoring the cells lost to the injury a...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2007.08.028
更新日期:2008-01-14 00:00:00
abstract::Diabetes mellitus (DM) ranks among the severest global health concerns of the 21st century. It encompasses a group of chronic disorders characterized by a dysregulated glucose metabolism, which arises as a consequence of progressive autoimmune destruction of pancreatic beta-cells (type 1 DM), or as a result of beta-ce...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.10.010
更新日期:2019-02-01 00:00:00
abstract::Drug resistance involves multiple mechanisms. Multidrug resistance (MDR) is the leading cause of treatment failure in cancer therapy. Elevated levels of MDR proteins [members of the ATP-binding cassette (ABC) transporter family] increase cellular efflux and decrease the effectiveness of chemotherapeutic agents. As a s...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2010.07.008
更新日期:2010-10-30 00:00:00
abstract::Hydrogels have been used primarily in the pharmaceutical field as carriers for delivery of various drugs, peptides and proteins. These systems have included stimuli-responsive gels that exhibit reversible swelling behavior and hence can show modulated release in response to external stimuli such as pH, temperature, io...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(01)00246-0
更新日期:2002-01-17 00:00:00
abstract::Despite intensive surgical excision, radiation therapy, and chemotherapy, the current life expectancy for patients diagnosed with glioblastoma multiforme is only 12 to 15months. One of the approaches being explored to increase chemotherapeutic efficacy is to locally deliver chemotherapeutics encapsulated within degrad...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.04.008
更新日期:2015-08-30 00:00:00
abstract::Tip-enhanced Raman scattering (TERS) has become a powerful tool for nanoscale structural analysis for several branches of organic, inorganic, and biological chemistry. This highly sensitive technique enables molecular characterization with a lateral resolution far beyond Abbe's diffraction limit and correlates structu...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.06.007
更新日期:2015-07-15 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::Toll-like receptor 9 (TLR9) agonists have demonstrated substantial potential as vaccine adjuvants, and as mono- or combination therapies for the treatment of cancer and infectious and allergic diseases. Commonly referred to as CpG oligodeoxynucleotides (ODN), TLR9 agonists directly induce the activation and maturation...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2008.12.008
更新日期:2009-03-28 00:00:00
abstract::Sensorineural hearing loss (SNHL) is one of the most common diseases, accounting for about 90% of all hearing loss. Leading causes of SNHL include advanced age, ototoxic medications, noise exposure, inherited and autoimmune disorders. Most of SNHL is irreversible and managed with hearing aids or cochlear implants. Alt...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2016.01.004
更新日期:2017-01-01 00:00:00
abstract::Nanomaterials composed of plant viral components are finding their way into medical technology and health care, as they offer singular properties. Precisely shaped, tailored virus nanoparticles (VNPs) with multivalent protein surfaces are efficiently loaded with functional compounds such as contrast agents and drugs, ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.08.011
更新日期:2019-05-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) have been developed for a number of indications due to their regenerative and anti-inflammatory phenotypes and their utility is enhanced by the fact that allogeneic transplant is feasible with this cell type. Animal studies and early human cases indicate that this has the potential to be ...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2017.10.003
更新日期:2018-01-01 00:00:00
abstract::For poorly water soluble drugs, the amorphous state provides an avenue to enhance oral bioavailability. The preparation method, in addition to sample history, can dictate the nature and the stability of the amorphous phase. Conventionally, X-ray powder diffractometry is of limited utility for characterization, but str...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.12.013
更新日期:2016-05-01 00:00:00
abstract::Gelatin is a denatured, biodegradable protein obtained by acid and alkaline processing of collagen. This processing affects the electrical nature of collagen, yielding gelatin with different isoelectric points (IEPs). When mixed with positively or negatively charged gelatin, an oppositely charged protein will ionicall...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章
doi:10.1016/s0169-409x(97)00125-7
更新日期:1998-05-04 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::The mammalian immune system has evolved mechanisms to recognize and respond to 'danger' signals arising from pathogens. Among those danger signals are the unmethylated CpG dinucleotide motifs found in bacteria. At least some of the recognition of these sequences is through cellular components of the innate immune syst...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/s0169-409x(00)00090-9
更新日期:2000-11-15 00:00:00
abstract::Angiogenesis is indispensable for solid tumor expansion, and thus it has become a major target of cancer research and anti-cancer therapies. Deciphering the arcane actions of various cell populations during tumor angiogenesis requires sophisticated research models, which could capture the dynamics and complexity of th...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2014.05.006
更新日期:2014-12-15 00:00:00
abstract::Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain ins...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2018.03.006
更新日期:2018-02-01 00:00:00
abstract::Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loa...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2015.09.001
更新日期:2016-01-15 00:00:00
abstract::Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical trans...
journal_title:Advanced drug delivery reviews
pub_type: 杂志文章,评审
doi:10.1016/j.addr.2012.07.004
更新日期:2012-12-01 00:00:00