Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case

Ronca, Roberto; Sozzani, Silvano; Presta, Marco; Alessi, Patrizia

doi:10.1016/j.imbio.2009.06.005

Cited by 26 publications

(20 citation statements)

References 105 publications

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“…Current antibody conjugates include Antibody RNA Conjugates (ARCs) for delivery of siRNAs, 71 , 72 Antibody Antibiotic Conjugates (AACs) to target pathogens, 73 , 74 Antibody Fluorophore Conjugates (AFCs) for imaging and laboratory reagents, 50 and Protein Antibody Conjugates (PACs) for the treatment of cancer 75 - 77 . Site-specific conjugation can be explored for use with these conjugates and would likely improve their production, stability, and homogeneity (Fig.…”

Section: Applications Of Site-specific Antibody Conjugatesmentioning

confidence: 99%

Site-specific antibody drug conjugates for cancer therapy

Panowski

Bhakta

Raab

et al. 2013

mAbs

576

528

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Antibody therapeutics have revolutionized the treatment of cancer over the past two decades. Antibodies that specifically bind tumor surface antigens can be effective therapeutics; however, many unmodified antibodies lack therapeutic activity. These antibodies can instead be applied successfully as guided missiles to deliver potent cytotoxic drugs in the form of antibody drug conjugates (ADCs). The success of ADCs is dependent on four factors—target antigen, antibody, linker, and payload. The field has made great progress in these areas, marked by the recent approval by the US Food and Drug Administration of two ADCs, brentuximab vedotin (Adcetris®) and ado-trastuzumab emtansine (Kadcyla®). However, the therapeutic window for many ADCs that are currently in pre-clinical or clinical development remains narrow and further improvements may be required to enhance the therapeutic potential of these ADCs. Production of ADCs is an area where improvement is needed because current methods yield heterogeneous mixtures that may include 0–8 drug species per antibody molecule. Site-specific conjugation has been recently shown to eliminate heterogeneity, improve conjugate stability, and increase the therapeutic window. Here, we review and describe various site-specific conjugation strategies that are currently used for the production of ADCs, including use of engineered cysteine residues, unnatural amino acids, and enzymatic conjugation through glycotransferases and transglutaminases. In addition, we also summarize differences among these methods and highlight critical considerations when building next-generation ADC therapeutics.

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Section: Applications Of Site-specific Antibody Conjugatesmentioning

confidence: 99%

Site-specific antibody drug conjugates for cancer therapy

Panowski

Bhakta

Raab

et al. 2013

mAbs

576

528

View full text Add to dashboard Cite

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“…They are large glycoproteins involved in cell adhesion and migration, and their expression is associated with a number of cancer-related biological processes. Due to specific expression in tumor cells, EDA and EDB have been extensively used in therapeutic studies for various cancers as targets of different agents, such as peptides, siRNAs, and antibodies [100,101,102,103]. The Philadelphia chromosome is a translocation between the ABL1 gene on chromosome 9 and the BCR gene on chromosome 22, leading to the formation of a constitutively active hybrid tyrosine kinase that contributes to the development of leukemia, especially chronic myelogenous leukemia (CML).…”

Section: Clinical Application Of Alternative Splicing In Cancer Thmentioning

confidence: 99%

From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform

Tian

Shi

et al. 2017

IJMS

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Alternative pre-mRNA splicing is a crucial process that allows the generation of diversified RNA and protein products from a multi-exon gene. In tumor cells, this mechanism can facilitate cancer development and progression through both creating oncogenic isoforms and reducing the expression of normal or controllable protein species. We recently demonstrated that an alternative cyclin D-binding myb-like transcription factor 1 (DMTF1) pre-mRNA splicing isoform, DMTF1β, is increasingly expressed in breast cancer and promotes mammary tumorigenesis in a transgenic mouse model. Aberrant pre-mRNA splicing is a typical event occurring for many cancer-related functional proteins. In this review, we introduce general aberrant pre-mRNA splicing in cancers and discuss its therapeutic application using our recent discovery of the oncogenic DMTF1 isoform as an example. We also summarize new insights in designing novel targeting strategies of cancer therapies based on the understanding of deregulated pre-mRNA splicing mechanisms.

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“…The established idea is that the simultaneous inhibition of angiogenesis, cancer cells and possibly the tumor supporting stroma would gain better results in fighting the disease. To this purpose several antibodies derived from phage display, targeting tumor overexpressed cytokines (e.g., GC-1008, an anti-Transforming Growth Factor β cytokine [152]), tumor stromal antigens (e.g., L19, an anti-isoform B of fibronectin [153]), or tumor-associated antigens (e.g., adecatumumab, that recognize epithelial cell-adhesion molecules [154]) are currently in clinical trials. Furthermore, once the target is really narrowed by the antigen recognition property of the antibody, the conjugation of the latter with cytotoxic or immunomodulatory drugs will strongly increase the therapeutic benefit for patients while reducing systemic drug toxicity [155].…”

Section: Clinical Studiesmentioning

confidence: 99%

Phage Displayed Peptides/Antibodies Recognizing Growth Factors and Their Tyrosine Kinase Receptors as Tools for Anti-Cancer Therapeutics

Ronca

Benzoni²,

Luca³

et al. 2012

IJMS

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The basic idea of displaying peptides on a phage, introduced by George P. Smith in 1985, was greatly developed and improved by McCafferty and colleagues at the MRC Laboratory of Molecular Biology and, later, by Barbas and colleagues at the Scripps Research Institute. Their approach was dedicated to building a system for the production of antibodies, similar to a naïve B cell repertoire, in order to by-pass the standard hybridoma technology that requires animal immunization. Both groups merged the phage display technology with an antibody library to obtain a huge number of phage variants, each of them carrying a specific antibody ready to bind its target molecule, allowing, later on, rare phage (one in a million) to be isolated by affinity chromatography. Here, we will briefly review the basis of the technology and the therapeutic application of phage-derived bioactive molecules when addressed against key players in tumor development and progression: growth factors and their tyrosine kinase receptors.

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Delivering cytokines at tumor site: The immunocytokine-conjugated anti-EDB-fibronectin antibody case

Cited by 26 publications

References 105 publications

Site-specific antibody drug conjugates for cancer therapy

Site-specific antibody drug conjugates for cancer therapy

From General Aberrant Alternative Splicing in Cancers and Its Therapeutic Application to the Discovery of an Oncogenic DMTF1 Isoform

Phage Displayed Peptides/Antibodies Recognizing Growth Factors and Their Tyrosine Kinase Receptors as Tools for Anti-Cancer Therapeutics

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