Chien-Tsun Kuan

Journal article Clin Cancer Res · August 1, 2018 Purpose: Conventional therapy for malignant glioma fails to specifically target tumor cells. In contrast, substantial evidence indicates that if appropriately redirected, T cells can precisely eradicate tumors. Here we report the rational development of a ... Full text Link to item Cite

Production and quality control assessment of a GLP-grade immunotoxin, D2C7-(scdsFv)-PE38KDEL, for a phase I/II clinical trial.

Journal article Appl Microbiol Biotechnol · April 2017 D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initia ... Full text Link to item Cite

In Vivo Selection Against Human Colorectal Cancer Xenografts Identifies an Aptamer That Targets RNA Helicase Protein DHX9.

Journal article Mol Ther Nucleic Acids · April 26, 2016 The ability to selectively target disease-related tissues with molecules is critical to the design of effective therapeutic and diagnostic reagents. Recognizing the differences between the in vivo environment and in vitro conditions, we employed an in vivo ... Full text Link to item Cite

Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats.

Journal article Invest New Drugs · April 2016 D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel immunotoxin that reacts with wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFRvIII proteins overexpressed in glioblastomas. This study assessed the toxicity of intracerebral administration of D2 ... Full text Link to item Cite

EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss.

Journal article Clin Cancer Res · February 15, 2014 PURPOSE: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to ... Full text Link to item Cite

Rational design and generation of recombinant control reagents for bispecific antibodies through CDR mutagenesis.

Journal article J Immunol Methods · September 30, 2013 Developments in the field of bispecific antibodies have progressed rapidly in recent years, particularly in their potential role for the treatment of malignant disease. However, manufacturing stable molecules has proven to be costly and time-consuming, whi ... Full text Link to item Cite

Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.

Journal article Clin Cancer Res · September 1, 2013 PURPOSE: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive wi ... Full text Link to item Cite

Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors.

Journal article Int J Cancer · May 15, 2013 Our study demonstrates the glioma tumor antigen podoplanin to be present at very high levels (>90%) in both glioblastoma (D2159MG, D08-0308MG and D08-0493MG) and medulloblastoma (D283MED, D425MED and DAOY) xenografts and cell line. We constructed a novel r ... Full text Link to item Cite

Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma.

Journal article Proc Natl Acad Sci U S A · January 2, 2013 Bispecific antibodies (bscAbs), particularly those of the bispecific T-cell engager (BiTE) subclass, have been shown to effectively redirect T cells against cancer. Previous efforts to target antigens expressed in both tumors and normal tissues have produc ... Full text Link to item Cite

Affinity-matured recombinant immunotoxin targeting gangliosides 3'-isoLM1 and 3',6'-isoLD1 on malignant gliomas.

Journal article MAbs · 2013 About 60 percent of glioblastomas highly express the gangliosides 3'-isoLM1 and 3',6'-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the ... Full text Link to item Cite

Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma.

Journal article Hum Gene Ther · October 2012 No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have ... Full text Link to item Cite

Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors.

Journal article Nucl Med Biol · January 2012 INTRODUCTION: Malignant glioma remains a significant therapeutic challenge, and immunotherapeutics might be a beneficial approach for these patients. A monoclonal antibody (MAb) specific for multiple molecular targets could expand the treatable patient pop ... Full text Link to item Cite

Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas.

Journal article Int J Cancer · July 1, 2011 Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mut ... Full text Link to item Cite

Bispecific antibodies engage T cells for antitumor immunotherapy.

Journal article Expert Opin Biol Ther · July 2011 INTRODUCTION: Although considerable evidence supports the hypothesis that T cells play a critical role in the immune response against cancer, the ability to mount and sustain tumor-specific cellular responses in vivo remains a challenge. A strategy that ha ... Full text Link to item Cite

Multiple phenotypic changes in mice after knockout of the B3gnt5 gene, encoding Lc3 synthase--a key enzyme in lacto-neolacto ganglioside synthesis.

Journal article BMC Dev Biol · November 18, 2010 BACKGROUND: Ganglioside biosynthesis occurs through a multi-enzymatic pathway which at the lactosylceramide step is branched into several biosynthetic series. Lc3 synthase utilizes a variety of galactose-terminated glycolipids as acceptors by establishing ... Full text Open Access Link to item Cite

Evaluation of anti-podoplanin rat monoclonal antibody NZ-1 for targeting malignant gliomas.

Journal article Nucl Med Biol · October 2010 INTRODUCTION: Podoplanin/aggrus is a mucin-like sialoglycoprotein that is highly expressed in malignant gliomas. Podoplanin has been reported to be a novel marker to enrich tumor-initiating cells, which are thought to resist conventional therapies and to b ... Full text Link to item Cite

Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation.

Journal article Oncogene · September 16, 2010 Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered ... Full text Link to item Cite

MRP3: a molecular target for human glioblastoma multiforme immunotherapy.

Journal article BMC Cancer · September 1, 2010 BACKGROUND: Glioblastoma multiforme (GBM) is refractory to conventional therapies. To overcome the problem of heterogeneity, more brain tumor markers are required for prognosis and targeted therapy. We have identified and validated a promising molecular th ... Full text Open Access Link to item Cite

Recombinant single-chain variable fragment antibodies against extracellular epitopes of human multidrug resistance protein MRP3 for targeting malignant gliomas.

Journal article Int J Cancer · August 1, 2010 Multidrug resistance protein 3 (MRP3), a multidrug resistance protein identified by serial analysis of gene expression as a glioblastoma multiforme (GBM)-associated molecule, is highly expressed in GBM, but not in normal brain cells. Thus, MRP3 is a candid ... Full text Link to item Cite

GMab-1, a high-affinity anti-3'-isoLM1/3',6'-isoLD1 IgG monoclonal antibody, raised in lacto-series ganglioside-defective knockout mice.

Journal article Biochem Biophys Res Commun · January 1, 2010 The lacto-series gangliosides 3'-isoLM1 and 3',6'-isoLD1 have been identified as tumor-associated antigens whose formation is initiated by the Lc3-synthase. Until now, high-affinity IgG monoclonal antibodies (mAbs) against 3'-isoLM1 and 3',6'-isoLD1, which ... Full text Link to item Cite

A monoclonal antibody IMab-1 specifically recognizes IDH1R132H, the most common glioma-derived mutation.

Journal article Biochem Biophys Res Commun · December 18, 2009 IDH1 (isocitrate dehydrogenase 1) mutations have been identified as early and frequent genetic alterations in astrocytomas, oligodendrogliomas, and oligoastrocytomas as well as secondary glioblastomas. In contrast, primary glioblastomas very rarely contain ... Full text Link to item Cite

Detection of amino-terminal extracellular domain of somatostatin receptor 2 by specific monoclonal antibodies and quantification of receptor density in medulloblastoma.

Journal article Hybridoma (Larchmt) · December 2009 Somatostatin receptor 2 (SSTR2) is expressed by most medulloblastomas (MEDs). We isolated monoclonal antibodies (MAbs) to the 12-mer (33)QTEPYYDLTSNA(44), which resides in the extracellular domain of the SSTR2 amino terminus, screened the peptide-bound MAb ... Full text Open Access Link to item Cite

Aptamers selected against the unglycosylated EGFRvIII ectodomain and delivered intracellularly reduce membrane-bound EGFRvIII and induce apoptosis.

Journal article Biol Chem · February 2009 Epidermal growth factor receptor variant III (EGFRvIII) is a glycoprotein uniquely expressed in glioblastoma, but not in normal brain tissues. To develop targeted therapies for brain tumors, we selected RNA aptamers against the histidine-tagged EGFRvIII ec ... Full text Link to item Cite

Synergistic control of T cell development and tumor suppression by diacylglycerol kinase alpha and zeta.

Journal article Proc Natl Acad Sci U S A · August 19, 2008 Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosphatidic acid (PA), the physiologic functions of which have been poorly defined. We report here that DGK alpha and zeta synergistically promote T cell maturation in the thy ... Full text Link to item Cite

EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells.

Journal article Cancer Immunol Immunother · January 2008 PURPOSE: Immunotoxins as anti-cancer therapeutics have several potential advantages over conventional agents including a high specificity, extraordinary potency, and a lack of an identified mechanism for resistance. It has been clearly demonstrated that Ps ... Full text Link to item Cite

Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme.

Journal article Clin Cancer Res · April 1, 2006 PURPOSE: More brain tumor markers are required for prognosis and targeted therapy. We have identified and validated promising molecular therapeutic glioblastoma multiforme (GBM) targets: human transmembrane glycoprotein nonmetastatic melanoma protein B (GP ... Full text Link to item Cite

Antiepidermal growth factor variant III scFv fragment: effect of radioiodination method on tumor targeting and normal tissue clearance.

Journal article Nucl Med Biol · January 2006 INTRODUCTION: MR1-1 is a single-chain Fv (scFv) fragment that binds with high affinity to epidermal growth factor receptor variant III, which is overexpressed on gliomas and other tumors but is not present on normal tissues. The objective of this study was ... Full text Link to item Cite

Monoclonal antibodies for brain tumour treatment.

Journal article Expert Opin Biol Ther · September 2004 Conventional treatment of brain tumours includes surgical, radiotherapeutic and chemotherapeutic modalities. Nonetheless, the outcome of patients with brain tumours, in particular glioblastoma, remains poor. Immunotherapy with armed or unarmed monoclonal a ... Full text Link to item Cite

Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model.

Journal article J Biol Chem · May 2, 2003 We employed a genetically defined human cancer model to investigate the contributions of two genes up-regulated in several cancers to phenotypic changes associated with late stages of tumorigenesis. Specifically, tumor cells expressing two structurally unr ... Full text Link to item Cite

EGF mutant receptor vIII as a molecular target in cancer therapy.

Journal article Endocr Relat Cancer · June 2001 Full text Link to item Cite

Increased binding affinity enhances targeting of glioma xenografts by EGFRvIII-specific scFv.

Journal article Int J Cancer · December 15, 2000 Combinatorial variation of CDR3 of V(H) and V(L), followed by phage display, was used to select affinity mutants of the parental anti-epidermal growth factor receptor-vIII (EGFRvIII) scFv MR1. One mutant, MR1-1(scFv), had increased specific binding affinit ... Full text Link to item Cite

Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.

Journal article J Clin Oncol · November 15, 2000 PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any ob ... Full text Link to item Cite

Design of a novel small peptide targeted against a tumor-specific receptor.

Journal article Biochem Biophys Res Commun · August 28, 2000 EGFRvIII is the most common deletion variant of the epidermal growth factor receptor and is found in cancers of the brain, breast, ovary, and lung. The complete absence of the receptor in healthy tissues makes it an ideal tumor marker. We sought to design ... Full text Link to item Cite

EGFRvIII as a promising target for antibody-based brain tumor therapy.

Journal article Brain Tumor Pathol · 2000 Cell surface receptors are attractive candidates for targeted therapy of cancer. Growth factors and their receptors play important roles in the regulation of cell division, development, and differentiation. Among those, the epidermal growth factor receptor ... Full text Link to item Cite

Regional treatment of epidermal growth factor receptor vIII-expressing neoplastic meningitis with a single-chain immunotoxin, MR-1.

Journal article Clin Cancer Res · September 1999 The incidence of neoplastic meningitis is on the rise. Neoplastic meningitis can result from a direct seeding of the neuraxis by primary brain tumors or by hematogeneous spread of systemic solid tumors. A frequent genetic alteration in primary brain tumors ... Link to item Cite

125I-labeled anti-epidermal growth factor receptor-vIII single-chain Fv exhibits specific and high-level targeting of glioma xenografts.

Journal article Clin Cancer Res · June 1999 A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a d ... Link to item Cite

¹²⁵I-labeled anti-epidermal growth factor receptor-vIII single-chain Fv exhibits specific and high-level targeting of glioma xenografts

Journal article Clinical Cancer Research · 1999 A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a d ... Cite

Recombinant heregulin-Pseudomonas exotoxin fusion proteins: interactions with the heregulin receptors and antitumor activity in vivo.

Journal article Clin Cancer Res · April 1998 Growth factor receptors provide unique opportunities for development of targeted anticancer therapy. Members of the type I receptor tyrosine kinase family, including epidermal growth factor (EGF) receptor (EGFR) and ErbB-2/neu, are often overexpressed in v ... Link to item Cite

Recombinant immunotoxin containing a disulfide-stabilized Fv directed at erbB2 that does not require proteolytic activation.

Journal article Biochemistry · March 5, 1996 PE35/e23(dsFv)KDEL is a recombinant immunotoxin composed of a recombinant form of Pseudomonas exotoxin that does not need proteolytic activation and a disulfide-stabilized Fv fragment of the anti-erbB2 monoclonal antibody e23. In this molecule, the variabl ... Full text Link to item Cite

Improved antitumor activity of a recombinant anti-Lewis(y) immunotoxin not requiring proteolytic activation.

Journal article Proc Natl Acad Sci U S A · February 6, 1996 B1(dsFv)-PE33 is a recombinant immunotoxin composed of a mutant form of Pseudomonas exotoxin (PE) that does not need proteolytic activation and a disulfide-stabilized Fv fragment of the anti-Lewis(y) monoclonal antibody B1, which recognizes a carbohydrate ... Full text Link to item Cite

Immunotoxins containing Pseudomonas exotoxin that target LeY damage human endothelial cells in an antibody-specific mode: relevance to vascular leak syndrome.

Journal article Clin Cancer Res · December 1995 Vascular leak syndrome (VLS) was originally found to be a major dose-limiting toxicity in humans with cancer treated with several immunotoxins (ITs) containing ricin A chain or blocked ricin. Recently, VLS has also been observed in patients treated with an ... Link to item Cite

Pseudomonas exotoxin A mutants. Replacement of surface exposed residues in domain II with cysteine residues that can be modified with polyethylene glycol in a site-specific manner.

Journal article J Biol Chem · March 11, 1994 Pseudomonas exotoxin A (PE) is a three-domain protein in which domain Ia is involved in recognition of receptors on eukaryotic target cells, domain II promotes translocation of PE into the cytosol, and domain III enzymatically ADP-ribosylates elongation fa ... Link to item Cite

Further evidence that transposition of Tn5 in Escherichia coli is strongly enhanced by constitutively activated RecA proteins.

Journal article J Bacteriol · November 1992 We have shown that excision and transposition of Tn5 in Escherichia coli are greatly increased by recA(Prtc) genes, which encode constitutively activated RecA proteins (C.-T. Kuan, S.-K. Liu, and I. Tessman, Genetics 128:45-57, 1991). Contrary results, sho ... Full text Link to item Cite

LexA protein of Escherichia coli represses expression of the Tn5 transposase gene.

Journal article J Bacteriol · October 1991 The LexA protein of Escherichia coli represses expression of a variety of genes that, by definition, constitute the SOS regulon. Genetic evidence suggests that Tn5 transposition is also regulated by the product of the lexA gene (C.-T. Kuan, S.-K. Liu, and ... Full text Link to item Cite

Excision and transposition of Tn5 as an SOS activity in Escherichia coli.

Journal article Genetics · May 1991 Excision and transposition of the Tn5 element in Escherichia coli ordinarily appear to occur by recA-independent mechanisms. However, recA(Prtc) genes, which encode RecA proteins that are constitutively activated to the protease state, greatly enhanced exc ... Full text Link to item Cite