A Pilot Study Assessing Safety and Tolerability of Lewis Y (LeY) targeting Chimeric Antigen Receptor (CAR) T cells in combination with Nivolumab in Patients With LeY Expressing Solid Tumours

Start Date17 Jan 2023

Sponsor / Collaborator

Peter MacCallum Cancer Institute

NCT04842812 / RecruitingPhase 1IIT

Engineered TILs/CAR-TILs With PD1 Knockout and Anti-PD1/CTLA4-scFv Secreting or CARs Against Various Antigens to Treat Advanced Solid Tumors

Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.

Start Date01 Jan 2021

Sponsor / Collaborator

Second Affiliated Hospital of Guangzhou Medical University

[+1]

100 Clinical Results associated with Lewis-Y antigen

100 Translational Medicine associated with Lewis-Y antigen

0 Patents (Medical) associated with Lewis-Y antigen

147

Literatures (Medical) associated with Lewis-Y antigen

01 Mar 2023·Biochimie

Purification and characterization of a hemocyanin with lectin-like activity isolated from the hemolymph of speckled shrimp, Metapenaeus monoceros

Article

Author: Dilna, C ; Soni, Priyanka ; Prasanth, Ganesh K ; Duddukuri, Govinda Rao ; Kanade, Santosh R ; Ghufran, Md Sajid

Lectins or agglutinins are mainly proteins or glycoproteins, reported to uphold an ability to agglutinate the red blood cells (RBCs) with a known sugar specificity in a diverse group of organisms. In the present study, we purified a hemocyanin (named as MmHc) from a shrimp, Metapenaeus monoceros by size-exclusion chromatography. Further characterization revealed that the purified MmHc showed hemagglutination activity that was found to be specifically inhibited by Lewis B and Lewis Y tetrasaccharides. The MmHc displayed two oligomers of molecular weight approximately ∼78 and ∼85 kDa in SDS-PAGE. The native molecular mass of MmHc was found to be ∼457 kDa as determined by size-exclusion chromatography which indicated that the purified MmHc is an oligomeric protein. MmHc showed a maximum activity within pH 7.0-8.0, while a wide range of temperature stability was observed between 4 to 55 °C, however, it did not show any dependency on metal ions for binding. Subsequently, the analysis of the peptides by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) identified the purified MmHc as shrimp hemocyanin showing significant similarity to the hemocyanin of Penaeus vannamei. The results of multiple sequence alignment and detailed analysis of the molecular interactions predicted by AutoDock suggested that besides the oxygen carrier function, this MmHc may have multiple roles and can interact well with the Lewis Y antigen through a typical sugar binding motif containing the similar hydrophilic amino acids as the conserved residues.

01 Mar 2023·JPMA. The Journal of the Pakistan Medical Association

X-ray inhibits FUT4-mediated proliferation in A549 cells by downregulating SP1 expression.

Article

Author: Gao, Wei ; Liang, Jin-Xiao ; Wei, Wei-Tian ; Liu, Jin-Shi ; Yang, Xun

ObjectiveTo identify the mechanism of down-regulation of Lewis Y antigen caused by X-ray irradiation.METHODSThe present original research study was conducted at Zhejiang University City College, Hangzhou, Republic of China, from 2020 to 2022. Western blotting, Co-immunoprecipitation (CO-IP), electrophoretic mobility shift assay and Cell Counting Kit-8 (CCK8) were performed to confirm the effect of X-ray irradiation on A549 cell proliferation and its mechanism. Data was analysed using Statistical Package for Social Sciences (SPSS) 11.5.RESULTSThe expressions of fucosyltransferase IV and Lewis Y were decreased after X-ray irradiation, thus inhibiting the proliferation of A549 lung cancer cells. Deoxyribonucleic acid damage caused by the irradiation caused higher level of poly- adenosinediphosphate-ribosylated Specific Protein 1(SP1), and translocation of SP1 from the nucleus, decreasing the expression of fucosyltransferase IV and Lewis Y.ConclusionThere was a significant role of glycosylation in radiation therapy for lung cancer.

23 May 2022·GlycobiologyQ3 · BIOLOGY

Characterization of five marine family 29 glycoside hydrolases reveals an α-L-fucosidase targeting specifically Fuc(α1,4)GlcNAc

Q3 · BIOLOGY

Article

Author: Teze, David ; Svensson, Birte ; Stougaard, Peter ; Schultz-Johansen, Mikkel

Abstract$\text{L} $ -Fucose is the most widely distributed $\text{L} $-hexose in marine and terrestrial environments and presents a variety of functional roles. $\text{L} $-Fucose is the major monosaccharide in the polysaccharide fucoidan from cell walls of brown algae and is found in human milk oligosaccharides (HMOs) and the Lewis blood group system, where it is important in cell signaling and immune response stimulation. Removal of fucose from these biomolecules is catalyzed by fucosidases belonging to different carbohydrate-active enzyme (CAZy) families. Fucosidases of glycoside hydrolase family 29 (GH29) release α-$\text{L} $-fucose from non-reducing ends of glycans and display activities targeting different substrate compositions and linkage types. While several GH29 fucosidases from terrestrial environments have been characterized, much less is known about marine members of GH29 and their substrate specificities, as only four marine GH29 enzymes were previously characterized. Here, five GH29 fucosidases originating from an uncultured fucoidan-degrading marine bacterium (Paraglaciecola sp.) were cloned and produced recombinantly in Escherichia coli. All five enzymes (Fp231, Fp239, Fp240, Fp251 and Fp284) hydrolyzed the synthetic substrate CNP-α-$\text{L} $-fucose. Assayed against up to 17 fucose-containing oligosaccharides, Fp239 showed activity against the Lewis Y antigen, 2′- and 3-fucosyllactose, while Fp284 degraded 2′-fucosyllactose and Fuc(α1,6)GlcNAc. Furthermore, Fp231 displayed strict specificity against Fuc(α1,4)GlcNAc, a previously unreported specificity in GH29. Fp231 is a monomeric enzyme with pH and temperature optima at pH 5.6–6.0 and 25°C, hydrolyzing Fuc(α1,4)GlcNAc with kcat = 1.3 s−1 and Km = 660 μM. Altogether, the findings extend our knowledge about GH29 family members from the marine environment, which are so far largely unexplored.

News (Medical) associated with Lewis-Y antigen

12 Jul 2023

·www.pharmaceutical-technology.com

Crossbow raises Series A funds to develop cancer antibodies

Crossbow Therapeutics will use the funds to develop therapies to treat cancer. Credit: crystal light via Shutterstock.com. Crossbow Therapeutics has raised Series A funds worth $80m to develop a new class of antibody treatments for cancer. MPM BioImpact and Pfizer Ventures led the funding round, with Polaris Partners, BVF Partners and Eli Lilly and Company among others taking part. Recommended Reports Reports LOA and PTSR Model - Vaccine For Oncology in Colorectal Cancer GlobalData Reports LOA and PTSR Model - Gene Therapy To Target Lewis Y Antigen For Lung Cancer in Lung Cancer GlobalData View all Companies Intelligence Eli Lilly and Co Polaris Partners LLC BVF Partners LP Crossbow Corp Pfizer Ventures LLC View all Proceeds will be used to progress the development of new therapies that act on peptide-loaded major histocompatibility complexes (pMHCs) present on cancer cells. To target pMHCs, these therapies will leverage antibodies that imitate T-cell receptors (TCR-mimetics). The company will identify, validate and select the most promising cancer-specific targets, then create TCR-mimetic antibodies that have greater levels of cancer cell affinity and specificity. Such TCR-mimetics will be merged with off-the-shelf T-cell engagers and immunotherapies to create tumour-bolt (T-Bolt) molecules. These T-Bolts can be tailored to treat a variety of cancers. Crossbow Therapeutics CEO Briggs Morrison stated: “With unparalleled accuracy and potency, our revolutionary T-Bolt products strike cancer cells like a crossbow shoots bolts at its target. “The influx of additional capital enables us to scale our efforts to build an arsenal of TCR-mimetic-based immunotherapies designed to overcome the limitations of current treatments.”

VaccineImmunotherapy

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Lewis-Y antigen

Basic Info

Related

Analysis