Isolation and characterization of monoclonal antibodies specific for chondroitin sulfate E

Watanabe, Ippei; Hikita, Tomoya; Mizuno, Haruka; Sekita, Risa; Minami, Akira; Ishii, Ami; Minamisawa, Yuka; Suzuki, Kiyoshi; Maéda, Hiroshi; Hidari, Kazuya I.P.J.; Suzuki, Takashi

doi:10.1093/glycob/cwv039

Cited by 15 publications

(24 citation statements)

References 30 publications

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“…Antibodies against different CS isoforms (CS-A, CS-C, and CS-E) exist but often their specificity toward the individual sulfation patterns is limited, or their epitope is rather small (1-2 disaccharides), leading to antibody crossreactivity with other similar sulfated isoforms (36)(37)(38)(39). The CS-E specific antibody GD3G7 also binds moderately to oversulfated dermatan sulfate (DS) from hagfish (IdoA-GalNac4S6S) and shark skin DS (40).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the antibody also recognizes IdoA, a component of dermatan sulfate and is not exclusively CS specific. A new CS-E specific antibody has recently been reported that can distinguish between iduronic and glucuronic acid and is, similar to D8, specific for CS (and not DS) (39). However, as the GAGs were mostly obtained commercially and purified from natural source, heterogeneity in the CS sulfation patterns is to be expected, i.e.…”

Section: Discussionmentioning

confidence: 99%

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Structure–function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8

Matho¹,

Schlossman²,

Gilchuk

et al. 2018

Journal of Biological Chemistry

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Vaccinia virus (VACV) envelope protein D8 is one of three glycosaminoglycan adhesion molecules and binds to the linear polysaccharide chondroitin sulfate (CS). D8 is also a target for neutralizing antibody responses that are elicited by the smallpox vaccine, which has enabled the first eradication of a human viral pathogen and is a useful model for studying antibody responses. However, to date, VACV epitopes targeted by human antibodies have not been characterized at atomic resolution. Here, we characterized the binding properties of several human anti-D8 antibodies and determined the crystal structures of three VACV-MAb variants, VACV-66, VACV-138, and VACV-304, separately bound to D8. While all these antibodies bound D8 with high affinity and were moderately neutralizing in the presence of complement, VACV-138 and VACV-304 also fully blocked D8 binding to CS-A, the low affinity ligand for D8. VACV-138 also abrogated D8 binding to the high-affinity ligand CS-E, but we observed residual CS-E binding was observed in the presence of VACV-304. Analysis of the VACV-138 and VACV-304 binding sites along the CS binding crevice of D8, combined with different efficiencies of blocking D8 adhesion to CS-A and CS-E allowed us to propose that D8 has a high and low affinity CS binding region within its central crevice. The crevice is amenable to protein engineering to further enhance both specificity and affinity of binding to CS-E. Finally, a wild-type D8 tetramer specifically bound to structures within the developing glomeruli of the kidney, which express CS-E. We propose that through structure-based protein engineering, an improved D8 tetramer Human antibody responses to vaccinia virus D82 could be used as a potential diagnostic tool to detect expression of CS-E, which is a possible biomarker for ovarian cancer.Smallpox is caused by infection with variola virus and was a major health threat until successful global vaccination efforts led to its complete eradication from the general human population (1). This eradication of an infectious agent was achieved by immunizing with Vaccinia virus (VACV), a related orthopoxvirus with low virulence and the active ingredient in the smallpox vaccine (2,3). Immunization with VACV leads to the robust production of highly neutralizing antibodies targeting several VACV envelope proteins, including A27, A33, B5, D8, H3, L1, and others, which are expressed on different viral envelopes (3,4). A27, D8, H3 and L1 are expressed on the outer membrane of the intracellular mature virion (IMV), while A33 and B5 are found in the more fragile extracellular enveloped virion (EEV), which has an additional host cell derived envelope. Both the IMV and the EEV particles are infectious virions, with IMV being more abundant and mainly responsible for spread between hosts, and EEV being involved in cell-to-cell spread within the host after infection with the IMV (5). As a result, a potent antibody-mediated immune response against VACV targets both infectious virions.Among the targeted envelope prote...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Structure–function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8

Matho¹,

Schlossman²,

Gilchuk

et al. 2018

Journal of Biological Chemistry

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“…Therefore, more focus on targeting the ECM may be an important breakthrough for OC [ 126 ]. Recently, CS-E was established to be overexpressed in OC ECM and made novel molecular target for anti-cancer therapy [ 115 , 129 ].…”

Section: Glycosaminoglycans As a Potential Molecular Target To Stomentioning

confidence: 99%

“…In 2015, Watanabe and co-workers [ 129 ] discovered two novel CS-E specific monoclonal antibodies, E-12C and E-18H. These antibodies were obtained by digesting CS-E fractions rich in the E subunits with hyaluronidase, susceptibly reacting with low sulphation moieties of the CS molecule.…”

Section: Glycosaminoglycans As a Potential Molecular Target To Stomentioning

confidence: 99%

“…To further verify this, E-12C and E-18H antibodies were reacted with an artificial CSH from DS possessing (IdoAβ1-3GalNAc (4S) resulting in no reacting ability of either antibody, concluding that these antibodies strictly recognize the E-unit (GlcAβ1-3GalNAc (4S, 6S)). Hence, these antibodies can distinguish the structural difference between GlcA and IdoA in the GAG molecules [ 129 ]. An important breakthrough for future of targeted therapy considerations.…”

Section: Glycosaminoglycans As a Potential Molecular Target To Stomentioning

confidence: 99%

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Nanotechnology and Glycosaminoglycans: Paving the Way Forward for Ovarian Cancer Intervention

Hoosen

Pradeep

Kumar

et al. 2018

IJMS

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Ovarian cancer (OC) has gained a great deal of attention due to its aggressive proliferative capabilities, high death rates and poor treatment outcomes, rendering the disease the ultimate lethal gynaecological cancer. Nanotechnology provides a promising avenue to combat this malignancy by the niche fabrication of optimally-structured nanomedicines that ensure potent delivery of chemotherapeutics to OC, employing nanocarriers to act as “intelligent” drug delivery vehicles, functionalized with active targeting approaches for precision delivery of chemotherapeutics to overexpressed biomarkers on cancer cells. Recently, much focus has been implemented to optimize these active targeting mechanisms for treatment/diagnostic purposes employing nanocarriers. This two-part article aims to review the latest advances in active target-based OC interventions, where the impact of the newest antibody, aptamer and folate functionalization on OC detection and treatment is discussed in contrast to the limitations of this targeting mechanism. Furthermore, we discuss the latest advances in nanocarrier based drug delivery in OC, highlighting their commercial/clinical viability of these systems beyond the realms of research. Lastly, in the second section of this review, we comprehensively discussed a focus shift in OC targeting from the well-studied OC cells to the vastly neglected extracellular matrix and motivate the potential for glycosaminoglycans (GAGs) as a more focused extracellular molecular target.

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Histological analysis of nucleus pulposus tissue from patients with lumbar disc herniation after condoliase administration

Minamisawa,

Shirogane,

Watanabe

et al. 2024

JOR Spine

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BackgroundCondoliase is an enzyme used as a treatment for lumbar disc herniation (LDH). This enzyme degrades chondroitin sulfate (CS) in the nucleus pulposus of the intervertebral disc (IVD). However, there are cases in which symptoms do not improve, despite condoliase administration. This study reports histological analysis of lumbar disc tissue of LDH patients who underwent surgery because condoliase had no therapeutic effect.MethodsBetween March 2019 and August 2019, 12 LDH patients who underwent full endoscopic spine surgery (FESS) discectomy at the Dezawa Akira PED Clinic were the subjects of the study. There are two study groups: six cases underwent FESS after condoliase administration, while six underwent FESS without condoliase administration. The average duration from drug administration to surgery was 152 days. Herniated disc removed at surgery was evaluated by histological staining including immunohistochemistry by anti‐CS antibodies.ResultsMultiple large clusters (40–120 μm in diameter) were observed in the nucleus pulposus of those who received condoliase, but no clusters were observed in those who did not. The lumbar disc tissues, including the nucleus pulposus of recipients, were stained with anti‐CS antibodies that recognize the CS unsaturated disaccharide, but non‐administration tissue was not stained. These findings suggest that the enzyme acted on the nucleus pulposus, even in cases where symptoms were not improved by condoliase administration. Furthermore, there was no histological difference between stained images of the extracellular matrix in those who did or did not receive condoliase, suggesting that condoliase acted specifically on CS in the nucleus pulposus.ConclusionsWe demonstrated that CS in the nucleus pulposus was degraded in patients in whom condoliase did not have a therapeutic effect. Moreover, condoliase acts in human IVD without causing necrosis of chondrocytes and surrounding tissues.

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Isolation and characterization of monoclonal antibodies specific for chondroitin sulfate E

Cited by 15 publications

References 30 publications

Structure–function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8

Structure–function characterization of three human antibodies targeting the vaccinia virus adhesion molecule D8

Nanotechnology and Glycosaminoglycans: Paving the Way Forward for Ovarian Cancer Intervention

Histological analysis of nucleus pulposus tissue from patients with lumbar disc herniation after condoliase administration

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