Keyword search (4,163 papers available)

"N RA" Authored Publications:

Title Authors PubMed ID
1 Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA) Chertkow H; Phillips N; Rockwood K; Anderson N; Andrew MK; Bartha R; Beaudoin C; Bélanger N; Bellec P; Belleville S; Bergman H; Best S; Bethell J; Bherer L; Black S; Borrie M; Camicioli R; Carrier J; Cashman N; Chan S; Crowshoe L; Cuello C; Cynader M; Dang-Vu T; Das S; Dixon RA; Ducharme S; Einstein G; Evans AC; Fahnestock M; Feldman H; Ferland G; Finger E; Fisk JD; Fogarty J; Fon E; Gan-Or Z; Gauthier S; Greenwood C; Henri-Bellemare C; Herrmann N; Hogan DB; Hsiung R; Itzhak I; Jacklin K; Lanctôt K; Lim A; MacKenzie I; Masellis M; Maxwell C; McAiney C; McGilton K; McLaurin J; Mihailidis A; Mohades Z; Montero-Odasso M; Morgan D; Naglie G; Nygaard H; O' Connell M; Petersen R; Pilon R; Rajah MN; Rapoport M; Roach P; Robillard JM; Rogaeva E; Rosa-Neto P; Rylett J; Sadavoy J; St George-Hyslop P; Seitz D; Smith E; Stefanovic B; Vedel I; Walker JD; Wellington C; Whitehead V; Wittich W; 39636028
HKAP
2 Cognitive Speed in Neurodegenerative Disease: Comparing Mean Rate and Inconsistency Within and Across the Alzheimer's and Lewy Body Spectra in the COMPASS-ND Study Caballero HS; McFall GP; Gee M; MacDonald S; Phillips NA; Fogarty J; Montero-Odasso M; Camicioli R; Dixon RA; 38875040
PSYCHOLOGY
3 Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22 McComb S; Arbabi-Ghahroudi M; Hay KA; Keller BA; Faulkes S; Rutherford M; Nguyen T; Shepherd A; Wu C; Marcil A; Aubry A; Hussack G; Pinto DM; Ryan S; Raphael S; van Faassen H; Zafer A; Zhu Q; Maclean S; Chattopadhyay A; Gurnani K; Gilbert R; Gadoury C; Iqbal U; Fatehi D; Jezierski A; Huang J; Pon RA; Sigrist M; Holt RA; Nelson BH; Atkins H; Kekre N; Yung E; Webb J; Nielsen JS; Weeratna RD; 38596311
BIOLOGY
4 Simulation of Capillary Hemodynamics and Comparison with Experimental Results of Microphantom Perfusion Weighted Imaging. S S, N RA 32637373
PHYSICS
5 The Comprehensive Assessment of Neurodegeneration and Dementia: Canadian Cohort Study. Chertkow H, Borrie M, Whitehead V, Black SE, Feldman HH, Gauthier S, Hogan DB, Masellis M, McGilton K, Rockwood K, Tierney MC, Andrew M, Hsiung GR, Camicioli R, Smith EE, Fogarty J, Lindsay J, Best S, Evans A, Das S, Mohaddes Z, Pilon R, Poirier J, Phillips NA, MacNamara E, Dixon RA, Duchesne S, MacKenzie I, Rylett RJ 31309917
PSYCHOLOGY
6 Author Correction: Building a global alliance of biofoundries. Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Feuvre RL, Friedman DC, Fu X, Gold ND, Herrgård MJ, Holowko MB, Johnson JR, Johnson RA, Keasling JD, Kitney RI, Kondo A, Liu C, Martin VJJ, Menolascina F, Ogino C, Patron NJ, Pavan M, Poh CL, Pretorius IS, Rosser SJ, Scrutton NS, Storch M, Tekotte H, Travnik E, Vickers CE, Yew WS, Yuan Y, Zhao H, Freemont PS 31296848
CHEMBIOCHEM
7 The priming effect of food persists following blockade of dopamine receptors. Evangelista C, Hantson A, Shams WM, Almey A, Pileggi M, Voisard JR, Boulos V, Al-Qadri Y, Gonzalez Cautela BV, Zhou FX, Duchemin J, Habrich A, Tito N, Koumrouyan RA, Patel S, Lorenc V, Gagne C, El Oufi K, Shizgal P, Brake WG 31350860
CSBN
8 Geo-referenced population-specific microsatellite data across American continents, the MacroPopGen Database. Lawrence ER, Benavente JN, Matte JM, Marin K, Wells ZRR, Bernos TA, Krasteva N, Habrich A, Nessel GA, Koumrouyan RA, Fraser DJ 30944329
BIOLOGY
9 Building a global alliance of biofoundries. Hillson N, Caddick M, Cai Y, Carrasco JA, Chang MW, Curach NC, Bell DJ, Le Feuvre R, Friedman DC, Fu X, Gold ND, Herrgård MJ, Holowko MB, Johnson JR, Johnson RA, Keasling JD, Kitney RI, Kondo A, Liu C, Martin VJJ, Menolascina F, Ogino C, Patron NJ, Pavan M, Poh CL, Pretorius IS, Rosser SJ, Scrutton NS, Storch M, Tekotte H, Travnik E, Vickers CE, Yew WS, Yuan Y, Zhao H, Freemont PS 31068573
CHEMBIOCHEM

 

Title:Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22
Authors:McComb SArbabi-Ghahroudi MHay KAKeller BAFaulkes SRutherford MNguyen TShepherd AWu CMarcil AAubry AHussack GPinto DMRyan SRaphael Svan Faassen HZafer AZhu QMaclean SChattopadhyay AGurnani KGilbert RGadoury CIqbal UFatehi DJezierski AHuang JPon RASigrist MHolt RANelson BHAtkins HKekre NYung EWebb JNielsen JSWeeratna RD
Link:https://pubmed.ncbi.nlm.nih.gov/38596311/
DOI:10.1016/j.omton.2024.200775
Publication:Molecular therapy. Oncology
Keywords:CAR optimizationCAR-TCD22MT: Regular Issuecell therapychimeric antigen receptorshematological malignancyleukemia and lymphomananobodypreclinical developmentsingle-domain antibody
PMID:38596311 Category: Date Added:2024-04-10
Dept Affiliation: BIOLOGY
1 Human Health Therapeutics Research Centre, National Research Council, Ottawa, ON, Canada.
2 Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
3 Centre for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON, Canada.
4 Terry Fox Laboratory, British Columbia Cancer Research Institute, Vancouver, BC, Canada.
5 Division of Hematology, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
6 Division of Anatomical Pathology, The Ottawa Hospital/University of Ottawa, Ottawa, ON, Canada.
7 University of Ottawa Faculty of Medicine, Ottawa, ON, Canada.
8 Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
9 Division of Hematopathology and Transfusion Medicine, The Ottawa Hospital/University of Ottawa, Ottawa, ON, Canada.
10 Department of Biology, Concordia University, Montréal, QC, Canada.
11 Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
12 Canada's Michael Smith Genome Sciences Centre, Vancouver, BC, Canada.
13 Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
14 Deeley Research Centre, British Columbia Cancer Research Institute, Victoria, BC, Canada.
15 Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
16 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Description:

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22. Immunization of an adult Llama glama with CD22 protein, sdAb-cDNA library construction, and phage panning yielded >20 sdAbs with diverse epitope and binding properties. Expressing CD22-sdAb-CAR in Jurkat cells drove varying CD22-specific reactivity not correlated with antibody affinity. Changing CD28- to CD8-transmembrane design increased CAR persistence and expression in vitro. CD22-sdAb-CAR candidates showed similar CD22-dependent CAR-T expansion in vitro, although only membrane-proximal epitope targeting CD22-sdAb-CARs activated direct cytolytic killing and extended survival in a lymphoma xenograft model. Based on enhanced survival in blinded xenograft studies, a lead CD22sdCAR-T was selected, achieving comparable complete responses to a benchmark short linker m971-scFv CAR-T in high-dose experiments. Finally, immunohistochemistry and flow cytometry confirm tissue and cellular-level specificity of the lead CD22-sdAb. This presents a complete report on preclinical development of a novel CD22sdCAR therapeutic.





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