LIVIVO - Search results -

Search results

Result 1 - 10 of total 52

Search options

Article ; Online: Next Generation Antibody Therapeutics Using Bispecific Antibody Technology.

Igawa, Tomoyuki

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2017 Volume 137, Issue 7, Page(s) 831–836

Abstract: Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody ... ...

Abstract	Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.
MeSH term(s)	Antibodies, Bispecific/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antigens, Neoplasm/immunology ; CD3 Complex/immunology ; Epitopes/immunology ; Factor IXa/immunology ; Factor X/immunology ; Hemophilia A/therapy ; Humans ; Hydrogen-Ion Concentration ; Immunoglobulin G ; Immunotherapy ; Neoplasms/therapy ; Protein Binding ; Protein Engineering/methods ; Solubility
Chemical Substances	Antibodies, Bispecific ; Antibodies, Monoclonal ; Antigens, Neoplasm ; CD3 Complex ; Epitopes ; Immunoglobulin G ; Factor X (9001-29-0) ; Factor IXa (EC 3.4.21.22)
Language	Japanese
Publishing date	2017
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.16-00252-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 643: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article: Electroretinographic and Optical Coherence Tomographic Evaluations of Eyes with Vitreoretinal Lymphoma.

Makita, Jun / Yoshikawa, Yuji / Kanno, Junji / Igawa, Yuro / Kumagai, Tomoyuki / Takano, Shunichiro / Katsumoto, Takeshi / Shoji, Takuhei / Shibuya, Masayuki / Shinoda, Kei

Journal of clinical medicine

2023 Volume 12, Issue 12

Abstract: Vitreoretinal lymphomas (VRLs) present with different clinical characteristics. However, only a few case reports have been published that evaluated the retinal function and the retinal morphology. The relationship between retinal morphology and function ... ...

Abstract	Vitreoretinal lymphomas (VRLs) present with different clinical characteristics. However, only a few case reports have been published that evaluated the retinal function and the retinal morphology. The relationship between retinal morphology and function of eyes with a vitreoretinal lymphoma (VRL) was investigated via optical coherence tomography (OCT) and electroretinography (ERG). The ERG and OCT findings in 11 eyes of 11 patients (69.4 ± 11.5 years old) who were diagnosed with VRL at the Saitama Medical University Hospital between December 2016 to May 2022 were studied. The decimal best-corrected visual acuity ranged from hand movements to 1.2 (median 0.2). Histopathological studies of the vitreous specimens showed class II VRL in one eye, class III VRL in seven eyes, class IV VRL in two eyes, and class V VRL in one eye. The IgH gene rearrangement was positive in three of the six eyes tested. The OCT images showed morphological abnormalities in 10 of the 11 (90.9%) eyes. Severe attenuation was found for the amplitudes of the b-wave of the DA 0.01 ERG in 6 of 11 eyes (54.5%), the DA 3.0 a-wave in 5 of 11 eyes (45.5%), the DA 3.0 b-wave in 36.4%, the LA 3.0 a-wave in 36.4%, the LA 3.0 b-wave in 18.2%, and flicker responses in 36.4% of the eyes. None of the DA 3.0 ERGs had a negative shape (b/a < 1.0). In the five eyes in which the a-wave was severely attenuated, hyperreflective dots were observed subretinally. The ERG analysis in eyes with a VRL indicates a relatively severe dysfunction of the outer retinal layer and was helpful in determining the site of the morphological changes in eyes with VRL.
Language	English
Publishing date	2023-06-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12123957
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Electroretinographic and Optical Coherence Tomographic Evaluations of Eyes with Vitreoretinal Lymphoma

Jun Makita / Yuji Yoshikawa / Junji Kanno / Yuro Igawa / Tomoyuki Kumagai / Shunichiro Takano / Takeshi Katsumoto / Takuhei Shoji / Masayuki Shibuya / Kei Shinoda

Journal of Clinical Medicine, Vol 12, Iss 3957, p

2023 Volume 3957

Abstract	Vitreoretinal lymphomas (VRLs) present with different clinical characteristics. However, only a few case reports have been published that evaluated the retinal function and the retinal morphology. The relationship between retinal morphology and function of eyes with a vitreoretinal lymphoma (VRL) was investigated via optical coherence tomography (OCT) and electroretinography (ERG). The ERG and OCT findings in 11 eyes of 11 patients (69.4 ± 11.5 years old) who were diagnosed with VRL at the Saitama Medical University Hospital between December 2016 to May 2022 were studied. The decimal best-corrected visual acuity ranged from hand movements to 1.2 (median 0.2). Histopathological studies of the vitreous specimens showed class II VRL in one eye, class III VRL in seven eyes, class IV VRL in two eyes, and class V VRL in one eye. The IgH gene rearrangement was positive in three of the six eyes tested. The OCT images showed morphological abnormalities in 10 of the 11 (90.9%) eyes. Severe attenuation was found for the amplitudes of the b-wave of the DA 0.01 ERG in 6 of 11 eyes (54.5%), the DA 3.0 a-wave in 5 of 11 eyes (45.5%), the DA 3.0 b-wave in 36.4%, the LA 3.0 a-wave in 36.4%, the LA 3.0 b-wave in 18.2%, and flicker responses in 36.4% of the eyes. None of the DA 3.0 ERGs had a negative shape (b/a < 1.0). In the five eyes in which the a-wave was severely attenuated, hyperreflective dots were observed subretinally. The ERG analysis in eyes with a VRL indicates a relatively severe dysfunction of the outer retinal layer and was helpful in determining the site of the morphological changes in eyes with VRL.
Keywords	intraocular lymphoma ; vitreoretinal lymphoma ; electroretinogram ; optical coherence tomography ; vitreous biopsy ; Medicine ; R
Subject code	290
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Improvement of pharmacokinetic properties of therapeutic antibodies by antibody engineering.

Haraya, Kenta / Tachibana, Tatsuhiko / Igawa, Tomoyuki

Drug metabolism and pharmacokinetics

2018 Volume 34, Issue 1, Page(s) 25–41

Abstract: Monoclonal antibodies (mAbs) have become an important therapeutic option for several diseases. Since several mAbs have shown promising efficacy in clinic, the competition to develop mAbs has become severe. In efforts to gain a competitive advantage over ... ...

Abstract	Monoclonal antibodies (mAbs) have become an important therapeutic option for several diseases. Since several mAbs have shown promising efficacy in clinic, the competition to develop mAbs has become severe. In efforts to gain a competitive advantage over other mAbs and provide significant benefits to patients, innovations in antibody engineering have aimed at improving the pharmacokinetic properties of mAbs. Because engineering can provide therapeutics that are more convenient, safer, and more efficacious for patients in several disease areas, it is an attractive approach to provide significant benefits to patients. Further advances in engineering mAbs to modulate their pharmacokinetics were driven by the increase of total soluble target antigen concentration that is often observed after injecting a mAb, which then requires a high dosage to antagonize. To decrease the required dosage, several antibody engineering techniques have been invented that reduce the total concentration of soluble target antigen. Here, we review the various ways that antibody engineering can improve the pharmacokinetic properties of mAbs.
MeSH term(s)	Animals ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/pharmacokinetics ; Biomedical Engineering/methods ; Biomedical Engineering/trends ; Drug Administration Routes ; Drug Administration Schedule ; Humans ; Metabolic Clearance Rate/drug effects ; Metabolic Clearance Rate/physiology ; Protein Binding/physiology ; Receptors, Fc/genetics ; Receptors, Fc/metabolism
Chemical Substances	Antibodies, Monoclonal ; Receptors, Fc
Language	English
Publishing date	2018-11-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2095748-8
ISSN	1880-0920 ; 1347-4367 ; 0916-1139
ISSN (online)	1880-0920
ISSN	1347-4367 ; 0916-1139
DOI	10.1016/j.dmpk.2018.10.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3734: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Humanization and Simultaneous Optimization of Monoclonal Antibody.

Kuramochi, Taichi / Igawa, Tomoyuki / Tsunoda, Hiroyuki / Hattori, Kunihiro

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1904, Page(s) 213–230

Abstract: Antibody humanization is an essential technology for reducing the potential risk of immunogenicity associated with animal-derived antibodies and has been applied to a majority of the therapeutic antibodies on the market. For developing an antibody ... ...

Abstract	Antibody humanization is an essential technology for reducing the potential risk of immunogenicity associated with animal-derived antibodies and has been applied to a majority of the therapeutic antibodies on the market. For developing an antibody molecule as a pharmaceutical at the current biotechnology level, however, other properties also have to be considered in parallel with humanization in antibody generation and optimization. This section describes the critical properties of therapeutic antibodies that should be sufficiently qualified, including immunogenicity, binding affinity, physicochemical stability, expression in host cells and pharmacokinetics, and the basic methodologies of antibody engineering involved. By simultaneously optimizing the antibody molecule in light of these properties, it should prove possible to shorten the research and development period necessary to identify a highly qualified clinical candidate and consequently accelerate the start of the clinical trial.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized/chemistry ; Antibodies, Monoclonal, Humanized/genetics ; Antibodies, Monoclonal, Humanized/immunology ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibody Affinity ; Antibody Specificity ; Gene Expression ; Humans ; Immunoglobulin Variable Region/chemistry ; Immunoglobulin Variable Region/genetics ; Immunoglobulin Variable Region/immunology ; Mice ; Mutation ; Protein Engineering ; Protein Stability ; Recombinant Proteins
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Immunoglobulin Variable Region ; Recombinant Proteins
Language	English
Publishing date	2018-12-11
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-8958-4_9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement.

Sampei, Zenjiro / Koo, Christine Xing'er / Teo, Frannie Jiuyi / Toh, Ying Xiu / Fukuzawa, Taku / Gan, Siok Wan / Nambu, Takeru / Ho, Adrian / Honda, Kiyofumi / Igawa, Tomoyuki / Ahmed, Fariyal / Wang, Cheng-I / Fink, Katja / Nezu, Junichi

Antibodies (Basel, Switzerland)

2023 Volume 12, Issue 2

Abstract: To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment ... ...

Abstract	To combat infectious diseases, vaccines are considered the best prophylactic strategy for a wide range of the population, but even when vaccines are effective, the administration of therapeutic antibodies against viruses could provide further treatment options, particularly for vulnerable groups whose immunity against the viruses is compromised. Therapeutic antibodies against dengue are ideally engineered to abrogate binding to Fcγ receptors (FcγRs), which can induce antibody-dependent enhancement (ADE). However, the Fc effector functions of neutralizing antibodies against SARS-CoV-2 have recently been reported to improve post-exposure therapy, while they are dispensable when administered as prophylaxis. Hence, in this report, we investigated the influence of Fc engineering on anti-virus efficacy using the anti-dengue/Zika human antibody SIgN-3C and found it affected the viremia clearance efficacy against dengue in a mouse model. Furthermore, we demonstrated that complement activation through antibody binding to C1q could play a role in anti-dengue efficacy. We also generated a novel Fc variant, which displayed the ability for complement activation but showed very low FcγR binding and an undetectable level of the risk of ADE in a cell-based assay. This Fc engineering approach could make effective and safe anti-virus antibodies against dengue, Zika and other viruses.
Language	English
Publishing date	2023-05-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661514-9
ISSN	2073-4468 ; 2073-4468
ISSN (online)	2073-4468
ISSN	2073-4468
DOI	10.3390/antib12020036
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Efficient production of bispecific antibody by FAST-Ig

Koga, Hikaru / Yamano, Takashi / Betancur, Juan / Nagatomo, Satoko / Ikeda, Yousuke / Yamaguchi, Kazuki / Nabuchi, Yoshiaki / Sato, Kazuki / Teranishi-Ikawa, Yuri / Sato, Motohiko / Hirayama, Hiroyuki / Hayasaka, Akira / Torizawa, Takuya / Haraya, Kenta / Sampei, Zenjiro / Shiraiwa, Hirotake / Kitazawa, Takehisa / Igawa, Tomoyuki / Kuramochi, Taichi

mAbs

2023 Volume 15, Issue 1, Page(s) 2222441

Abstract: Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To ... ...

Abstract	Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved > 95% correct HC/LC pairing efficiency with favorable pharmacological properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically.
MeSH term(s)	Animals ; Antibodies, Bispecific ; Hemophilia A ; Protein Engineering/methods ; Cell Line ; Dimerization ; Mammals
Chemical Substances	Antibodies, Bispecific
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2537838-7
ISSN	1942-0870 ; 1942-0870
ISSN (online)	1942-0870
ISSN	1942-0870
DOI	10.1080/19420862.2023.2222441
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Involvement of Mast-Cell-Tryptase- and Protease-Activated Receptor 2-Mediated Signaling and Urothelial Barrier Dysfunction with Reduced Uroplakin II Expression in Bladder Hyperactivity Induced by Chronic Bladder Ischemia in the Rat.

Akaihata, Hidenori / Matsuoka, Kanako / Hata, Junya / Harigane, Yuki / Yaginuma, Kei / Endo, Yu / Imai, Hitomi / Matsuoka, Yuta / Onagi, Akifumi / Tanji, Ryo / Honda-Takinami, Ruriko / Hoshi, Seiji / Koguchi, Tomoyuki / Sato, Yuichi / Kataoka, Masao / Uemura, Motohide / Igawa, Yasuhiko / Kojima, Yoshiyuki

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with ... ...

Abstract	We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured the expression of mast cell tryptase (MCT) and protease-activated receptor 2 (PAR2), which are correlated with C fiber activation via MCT, and Uroplakins (UP Ia, Ib, II and III), which are critical to urothelial barrier function, via Western blotting. The effects of FSLLRY-NH2, a PAR2 antagonist, administered intravenously, on the bladder function of CBI rats were evaluated with a cystometrogram. In the CBI group, the MC number in the bladder was significantly greater (
MeSH term(s)	Animals ; Rats ; Ischemia/metabolism ; Mast Cells/metabolism ; Receptor, PAR-2/metabolism ; Tryptases/metabolism ; Urinary Bladder/blood supply ; Urinary Bladder/metabolism ; Uroplakin II/metabolism ; Urothelium/metabolism ; Urinary Bladder, Overactive/metabolism
Chemical Substances	Receptor, PAR-2 ; Tryptases (EC 3.4.21.59) ; Uroplakin II
Language	English
Publishing date	2023-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24043982
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Sweeping antibody as a novel therapeutic antibody modality capable of eliminating soluble antigens from circulation.

Igawa, Tomoyuki / Haraya, Kenta / Hattori, Kunihiro

Immunological reviews

2016 Volume 270, Issue 1, Page(s) 132–151

Abstract: Monoclonal antibodies have become a general modality in therapeutic development, and a variety of monoclonal antibodies targeting soluble antigens have been developed. However, even with infinite binding affinity to an antigen, a conventional antibody ... ...

Abstract	Monoclonal antibodies have become a general modality in therapeutic development, and a variety of monoclonal antibodies targeting soluble antigens have been developed. However, even with infinite binding affinity to an antigen, a conventional antibody can bind to the antigen only once and results in an increase in total plasma antigen concentration in vivo. This antibody-mediated antigen accumulation generally occurs because the clearance from circulation of an antibody-antigen complex is much slower than that of a free antigen. This limitation has recently been overcome by sweeping antibodies, which are capable of actively eliminating soluble antigens from circulation. A sweeping antibody incorporates two antibody engineering technologies: one is variable region engineering to enable the antibody to bind to an antigen in plasma and dissociate from the antigen in endosome (after which the antigen undergoes lysosomal degradation), and the other is constant region engineering to increase the cellular uptake of the antibody-antigen complex into endosome. By enhancing the elimination of soluble antigens from circulation, sweeping antibodies can therapeutically target soluble antigens that conventional antibodies cannot. This review discusses the features, engineering technologies, advantages, and applications of sweeping antibodies that target soluble antigens.
MeSH term(s)	Animals ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/chemistry ; Antibodies, Neutralizing/genetics ; Antibodies, Neutralizing/immunology ; Antibodies, Neutralizing/therapeutic use ; Antibody Affinity/genetics ; Antibody Affinity/immunology ; Antibody Formation ; Antigens/blood ; Antigens/immunology ; Drug Discovery ; Genetic Engineering/methods ; Humans ; Protein Binding/immunology ; Receptors, Fc/metabolism
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antigens ; Receptors, Fc
Language	English
Publishing date	2016-03
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.12392
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Se 160: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Engineering CD3/CD137 dual specificity into a DLL3-targeted T-cell engager enhances T-cell infiltration and efficacy against small cell lung cancer.

Mikami, Hirofumi / Feng, Shu / Matsuda, Yutaka / Ishii, Shinya / Naoi, Sotaro / Azuma, Yumiko / Nagano, Hiroaki / Asanuma, Kentaro / Kayukawa, Yoko / Tsunenari, Toshiaki / Kamikawaji, Shogo / Iwabuchi, Ryutaro / Shinozuka, Junko / Yamazaki, Masaki / Kuroi, Haruka / Ho, Samantha Shu Wen / Gan, Siok Wan / Chichili, Priyanka / Pang, Chai Ling /

Yeo, Chiew Ying / Shimizu, Shun / Hironiwa, Naoka / Kinoshita, Yasuko / Shimizu, Yuichiro / Sakamoto, Akihisa / Muraoka, Masaru / Takahashi, Noriyuki / Kawa, Tatsuya / Shiraiwa, Hirotake / Mimoto, Futa / Kashima, Kenji / Kamata-Sakurai, Mika / Ishikawa, Shumpei / Aburatani, Hiroyuki / Kitazawa, Takehisa / Igawa, Tomoyuki

Cancer immunology research

2024

Abstract: Small cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICIs) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all SCLC patients are ... ...

Abstract	Small cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICIs) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all SCLC patients are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific). The CD3/CD137 dual-specific Fab was generated to competitively bind to CD3 and CD137 to prevent DLL3-independent cross-linking of CD3 and CD137, which could lead to systemic T-cell activation. We demonstrated that DLL3 trispecific induced better tumor growth control and a marked increase in the number of intratumoral T cells compared to a conventional DLL3-targeted bispecific T-cell engager. These findings suggest that DLL3 trispecific can exert potent efficacy by inducing concurrent CD137 costimulation and provide a promising therapeutic option for SCLC.
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-23-0638
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7022: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito