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UID:1158@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20230125T130000

DTEND;TZID=Asia/Jerusalem:20230125T140000

DTSTAMP:20230115T131359Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-inbar-
 arman/

SUMMARY:PhD Graduate Seminar- Inbar Arman [No Categories]
DESCRIPTION:Location:  hybrid- in the Faculty Auditorium/ZOOM: https://tech
 nion.zoom.us/j/99468656897  \n Affiliation: \n Host:Prof. Reiter Yoram\n I
 mmunomodulation of EAE with Antibodies Targeting Autoreactive T-Cell Epito
 pes\n\n&nbsp\;\n\nMultiple sclerosis (MS) is a demyelinating autoimmune di
 sease influencing more than 2.5 million people around the world. Damage ca
 used in this disease\, which is mediated by auto-reactive CD4+ T cells\, d
 isrupts nerve cell signaling\, resulting in variety of symptoms\, such as 
 blurred vision\, muscle stiffness and numbness. Previous studies suggested
  that human MS disease is associated with HLA-DR2 (DRB1*1501) MHC class II
  allele. Presentation of myelin associated epitopes\, such as myelin oligo
 dendrocyte glycoprotein (MOG) on HLA-DR2 by Antigen Presenting Cells (APCs
 ) to autoreactive CD4+ T cells in a pro-inflammatory context\, results in 
 autoreactive T cell activation and consequently demyelination and nerve ce
 lls damage. Since MHC:TCR interaction is the immune response core driving 
 force and is also the most specific check-point in the inflammatory proces
 s\,   targeting myelin associated epitopes presented in the context of M
 HC class II molecules by APCs may decrease myelin-specific autoreactive CD
 4+ T cell activation and consequently reduce the inflammatory process duri
 ng MS. This goal may be achieved using T cell receptor like (TCRL) antibod
 y- based (a) Chimeric Antigen Receptor (CAR) T cells\, targeted against my
 elin associated epitopes presented by APCs\, aiming for APCs destruction/s
 uppression or (b) TCRL-PDL1 conjugated molecule\, targeted against both PD
 1+ autoreactive T cells and myelin associated epitopes presented by APCs\,
  delivering specific immune response attenuation against self\, mediated b
 y the TCRL arm\, while inducing local autoreactive T cell inhibition via t
 he PD-L1 arm. Accordingly\, we have isolated and characterize TCRL antibod
 ies with specificity toward MOG/DR2 epitope and tested their MS therapeuti
 c effect as MOG/DR2-CAR-T cells and MOG/DR2-PDL1 bi-specific molecules. Ou
 r results suggests that anti-MOG/DR2-CD8+ CAR T cells show specific elimin
 ation of MOG/DR2 presenting APCs in-vitro\, but exacerbate disease symptom
 s in-vivo\, while anti-MOG/DR2 CAR T regulatory cells induce autoreactive 
 T cell inhibition ex-vivo and should be further examined in-vivo. Also\, a
 dministration of anti-MOG/DR2-PDL1 bi-specific molecules induce target-spe
 cific autoreactive T cell inhibition ex-vivo but shows inconclusive result
 s in-vivo and accordingly should be further optimized and examined as MS t
 herapeutic tool. 
LOCATION: hybrid- in the Faculty Auditorium/ZOOM: https://technion.zoom.us/
 j/99468656897

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DTSTART:20221030T010000

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