The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM) Complexes

Chang, Chien-Hsing; Rossi, Edmund A.; Wang, Yang; Goldenberg, David M.

doi:10.3390/antib2020353

Cited by 4 publications

(5 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Trop2 is overexpressed in chronic lymphocytic lymphoma (CLL), extranodal NK/T-cell lymphoma, nasal type (ENKTL), and non-Hodgkin's lymphoma (NHL) [ 12 , 56 , 57 ]. Trop2 is overexpressed in extranodal NK/T cell lymphoma, nasal type (ENKTL) and is associated with lymph node involvement and poor overall survival.…”

Section: Introductionmentioning

confidence: 99%

“…Trop2 is one of the antibodies used in the construction of bsHexAbs, bispecific hexavalent antibodies, which use the Dock-and-Lock (DNL) method for therapy of treating malignancies [ 56 ]. DNL is a method for building bioactive molecules with multifunctional structures [ 80 ].…”

Section: Introductionmentioning

confidence: 99%

“…The C K -format has advantages over the C H 3-format as revealed by preclinical results due to improved anti-lymphoma activity in vivo. BsHexAbs targets CD20 and CD22 in CLL and Raji Burkitt lymphoma cells and increases chances of survival based on mice xenograft experiments [ 56 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Trop2 and its overexpression in cancers: regulation and clinical/ therapeutic implications

2014

View full text Add to dashboard Cite

Trop2 is a transmembrane glycoprotein encoded by the Tacstd2 gene. It is an intracellular calcium signal transducer that is differentially expressed in many cancers. It signals cells for self-renewal, proliferation, invasion, and survival. It has stem cell-like qualities. Trop2 is expressed in many normal tissues, though in contrast, it is overexpressed in many cancers and the overexpression of Trop2 is of prognostic significance. Several ligands have been proposed that interact with Trop2. Trop2 signals the cells via different pathways and it is transcriptionally regulated by a complex network of several transcription factors. Trop2 expression in cancer cells has been correlated with drug resistance. Several strategies target Trop2 on cancer cells that include antibodies, antibody fusion proteins, chemical inhibitors, nanoparticles, etc. The in vitro studies and pre-clinical studies, using these various therapeutic treatments, have resulted in significant inhibition of tumor cell growth both in vitro and in vivo in mice. A clinical study is underway using IMMU-132 (hrS7 linked to SN38) in patients with epithelial cancers. This review describes briefly the various characteristics of cancer cells overexpressing Trop2 and the potential application of Trop2 as both a prognostic biomarker and as a therapeutic target to reverse resistance.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Trop2 and its overexpression in cancers: regulation and clinical/ therapeutic implications

2014

View full text Add to dashboard Cite

show abstract

“…Dual-drug targeting is another strategy which uses two different ligands, one of which guides the carrier to the site of action and the other ligand then binds to the target cells, for example combining integrin-targeting using RGD peptides (which help carrier to accumulate in tumor tissue through angiogenic vascular bed expressing integrins) along with transferrin [130] or neurophilin [131] (which bind the carrier to cancer cells) . Dualtargeting strategies either using tandem single-chain triplebodies, which hold two scFv regions and one trigfuture science group Review Vhora, Patil, Bhatt, Gandhi, Baradia & Misra ger molecule to affect effector-cell mediated activity [132] or using bispecific hexavalent antibodies developed by Dock-and-Lock™ platform may also find applications in cancer, autoimmune, and infectious diseases [133]. Further, identification of newer specific receptors will enable us to develop new targeting ligands such as aptamers, antibodies and so on, which can be exploited.…”

Section: Future Perspectivementioning

confidence: 99%

Receptor-targeted Drug delivery: Current Perspective and Challenges

et al. 2014

View full text Add to dashboard Cite

Receptor-targeted drug delivery has been extensively explored for active targeting. However, the scarce clinical applications of such delivery systems highlight the implicit hurdles in development of such systems. These hurdles begin with lack of knowledge of differential expression of receptors, their accessibility and identification of newer receptors. Similarly, ligand-specific challenges range from proper choice of ligand and conjugation chemistry, to release of drug/delivery system from ligand. Finally, nanocarrier systems, which offer improved loading, biocompatibility and reduced premature degradation, also face multiple challenges. This review focuses on understanding these challenges, and means to overcome such challenges to develop efficient, targeted drug-delivery systems.

show abstract

“…Antibody-dendrimer conjugates were successfully investigated producing anti-EGFR DOTA derived PAMAM dendrimers [11]. To further increase permeability, attempts in molecular engineering have been made to develop bispecific antibodies with lower molecular weight [45,46].…”

Section: Protein-based Carrier Systemmentioning

confidence: 99%

Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs

et al. 2014

View full text Add to dashboard Cite

Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities of current drug therapy. However, the efficacy of these strategies, in particular "personalized medicine", depends on precise information about individual target expression rates. Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology and thus bridges current knowledge to the clinical use. Moreover, nuclear medicine techniques provide therapeutic applications with tracers that behave like the diagnostic tracer. The advantages of radioiodination, still the most versatile radiolabeling strategy, and other labeled compounds comprising covalently attached radioisotopes are compared to the use of chelator-protein conjugates that are complexed with metallic radioisotopes. With the techniques using radioactive isotopes as a reporting unit or even the therapeutic principle, care has to be taken to avoid cleavage of the radionuclide from the protein it is linked to. The tracers used in molecular imaging require labeling techniques that provide site specific conjugation and metabolic stability. Appropriate choice of the radionuclide allows tailoring the properties of the labeled protein to the application required. Until the event of positron emission tomography the spectrum of nuclides used to visualize cellular and biochemical processes was largely restricted to iodine isotopes and 99m-technetium. Today, several nuclides such as 18-fluorine, 68-gallium and 86-yttrium have fundamentally extended the possibilities of tracer design and in turn caused the need for the development of chemical methods for their conjugation.

show abstract

The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM) Complexes

Cited by 4 publications

References 66 publications

Trop2 and its overexpression in cancers: regulation and clinical/ therapeutic implications

Trop2 and its overexpression in cancers: regulation and clinical/ therapeutic implications

Receptor-targeted Drug delivery: Current Perspective and Challenges

Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs

Contact Info

Product

Resources

About