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SUMMARY:Targeting altered immune-crosstalk in tissues to enhance immunity 
 - Prof Arne Akbar\; UCL Division of Biosciences
DTSTART:20220728T120000Z
DTEND:20220728T130000Z
UID:TALK176621@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Akbar has identified new mechanisms for immune decline in huma
 n ageing and has demonstrated unequivocally that targeting these age-assoc
 iated alterations can enhance human immunity in vivo. The importance of th
 ese new discoveries is underscored by infections by novel viruses\, that a
 ffect the older population disproportionately and these new findings offer
  the possibility to enhance anti-viral and anti-cancer immunity in old sub
 jects. He showed that antigen-specific  responses in old humans animals ca
 n be boosted by the inhibition of inflammation with small molecule inhibit
 ors in vivo. Akbar’s career in Immunology spans 40 years from his PhD to
  the present. In addition is group identified of a new multi-protein inhib
 itory complex that that actively maintains the reduced T cell activity in 
 old human as well as murine T cells and the inhibition of signalling via t
 his complex enhances T cells function. \n\nThe development of a novel expe
 rimental system for investigating human immunity during ageing in vivo. Mo
 st studies on human immunity are performed on leukocyte populations from p
 eripheral blood\, which do not reflect tissue-specific immune events. Akba
 r developed a unique experimental model to study immune responses in the s
 kin of human volunteers in vivo that involves the intradermal injection of
  viral antigens\, followed by the harvest of leukocytes from the challenge
  site by the induction and harvest of suction blisters or by taking skin b
 iopsies. An accelerated rate of telomere erosion was identified in T cells
  in the skin versus the blood after a single episode of antigen challenge\
 , associated with inhibition of telomerase activity by inflammatory cytoki
 nes\, including Type 1 IFN in situ. The cutaneous experimental system deve
 loped by Akbar has been adopted by pharmaceutical companies including GSK 
 and has been the cornerstone of international collaborations with the Univ
 ersity of Arizona\, the Rockefeller University in New York and the Nationa
 l University of Singapore. \nDiscovery of a multi-protein\, inhibitory com
 plex in aged T cells. The Akbar Group showed that inhibition of sestrins i
 n highly differentiated T cells from old humans significantly enhanced ant
 i-virus-specific activity in vitro.  Furthermore\, response to vaccination
  against influenza was significantly increased in aged sestrin knockout mi
 ce compared to old controls\, and both T cell and antibody responses were 
 enhanced. Although inhibition of individual MAP kinases in old mice had no
  effect on the influenza vaccine response\, inhibition of all 3 MAP kinase
 s simultaneously re-capitulated the enhanced responsiveness that was obser
 ved tin the sestrin deficient animals. This indicates a pathway for interv
 ention to enhance immunity during ageing in humans.\n\nInteraction with th
 e pharmaceutical industry. The Akbar group showed that inhibition of infla
 mmation by treatment of old volunteers with a clinical grade anti-inflamma
 tory p38 MAPkinase inhibitor (GSK\; Losmapimod significantly enhanced the 
 response to antigen challenge immunity in the skin of these healthy old su
 njects. This has considerable therapeutic implications e.g. enhancement of
  vaccine and anti-tumour responses in the elderly. This was funded by a MR
 C Grand Challenge in Experimental Medicine Grant (Akbar PI). Akbar is also
  involved in the development of the widely used anti-rejection drug for so
 lid organ transplants Basiliximab (Simulect) by Novartis. He produced key 
 data on which the patent was based. This drug has been used in the treatme
 nt of >300\,000 patients worldwide and has generated >£25 million in roya
 lty income to UCL. \n\nClick here to join live - https://us06web.zoom.us/j
 /87563440062 
LOCATION:Online via zoom &amp\; Kings Hedges Room 
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