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UID:1040@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20220126T130000

DTEND;TZID=Asia/Jerusalem:20220126T140000

DTSTAMP:20220117T111224Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-abraha
 m-rutenberg/

SUMMARY:PhD. Graduate Seminar- Abraham Rutenberg [No Categories]
DESCRIPTION:Location: Faculty of Bilogy Auditorium  \n Affiliation: \n Host
 :\n Tcell starvation and nutrient competition at the tumor micro environme
 nt is considered a major limiting factor in cancer immunotherapy. Metaboli
 c suppression hampers T cell activation\, differentiation\, and effector f
 unctions\, leading to T cell anergy and apoptosis\, resulting in tumor esc
 ape and immunotherapy failure. We propose a novel nanotechnology-based app
 roach to overcome metabolic T cell suppression: specific feeding of T cell
 s with nanoparticles encapsulating essential metabolites during the ex-viv
 o phase of adoptive CAR Tor TIL therapy. This creates an internal cellular
  reservoir of controlled release nutrients that will support T cell metabo
 lic requirements upon reaching the nutrient-depleted tumor microenvironmen
 t. In order to achieve high metabolite loading\, we use a core-shell archi
 tecture in which we polymerize a nano-meter silica shell on a nano-sized c
 ore of the desired metabolite obtained by grinding. By controlling the sol
 -gel synthesis parameters we can tailor shell thickness and porosity and d
 etermine metabolite release rate and encapsulation efficiency. Our prelimi
 nary work focuses on L-arginine as a model system – one of the keys most
  important amino acids for T cell activation depleted at the tumor microen
 vironment of many cancers. We generate arginine-loaded nanoparticles and d
 emonstrated arginine-controlled release kinetics. In order to enable T cel
 l uptake\, we conjugate anti-CD3 antibodies to the nanoparticle surface. F
 inally\, we demonstrate that arginine starvation leads to inhibition of T 
 cell proliferation\, reduced activation markers expression\, and impaired 
 survival\; while prior feeding of the T cells with arginine-encapsulating 
 nanoparticles partially rescues the activation phenotype. Based on these p
 reliminary results we propose that feeding T cells with metabolite encapsu
 lating nanoparticles may potentially relieve metabolic immune suppression 
 in adoptive cell therapies and result in superior CAR T andTIL cancer immu
 notherapies. 
LOCATION:Faculty of Bilogy Auditorium

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DTSTART:20211031T010000

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TZOFFSETTO:+0200

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