Development of a bispecific immune engager using a recombinant malaria protein
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Development of a bispecific immune engager using a recombinant malaria protein. / Nordmaj, Mie A.; Roberts, Morgan E.; Sachse, Emilie S.; Dagil, Robert; Andersen, Anne Poder; Skeltved, Nanna; Grunddal, Kaare V.; Erdoğan, Sayit Mahmut; Choudhary, Swati; Gustavsson, Tobias; Ørum-madsen, Maj Sofie; Moskalev, Igor; Tian, Weihua; Yang, Zhang; Clausen, Thomas M.; Theander, Thor G.; Daugaard, Mads; Nielsen, Morten A.; Salanti, Ali.
I: Cell Death & Disease, Bind 12, Nr. 4, 353, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Development of a bispecific immune engager using a recombinant malaria protein
AU - Nordmaj, Mie A.
AU - Roberts, Morgan E.
AU - Sachse, Emilie S.
AU - Dagil, Robert
AU - Andersen, Anne Poder
AU - Skeltved, Nanna
AU - Grunddal, Kaare V.
AU - Erdoğan, Sayit Mahmut
AU - Choudhary, Swati
AU - Gustavsson, Tobias
AU - Ørum-madsen, Maj Sofie
AU - Moskalev, Igor
AU - Tian, Weihua
AU - Yang, Zhang
AU - Clausen, Thomas M.
AU - Theander, Thor G.
AU - Daugaard, Mads
AU - Nielsen, Morten A.
AU - Salanti, Ali
PY - 2021
Y1 - 2021
N2 - As an immune evasion and survival strategy, the Plasmodium falciparum malaria parasite has evolved a protein named VAR2CSA. This protein mediates sequestration of infected red blood cells in the placenta through the interaction with a unique carbohydrate abundantly and exclusively present in the placenta. Cancer cells were found to share the same expression of this distinct carbohydrate, termed oncofetal chondroitin sulfate on their surface. In this study we have used a protein conjugation system to produce a bispecific immune engager, V-aCD3, based on recombinant VAR2CSA as the cancer targeting moiety and an anti-CD3 single-chain variable fragment linked to a single-chain Fc as the immune engager. Conjugation of these two proteins resulted in a single functional moiety that induced immune mediated killing of a broad range of cancer cells in vitro and facilitated tumor arrest in an orthotopic bladder cancer xenograft model.
AB - As an immune evasion and survival strategy, the Plasmodium falciparum malaria parasite has evolved a protein named VAR2CSA. This protein mediates sequestration of infected red blood cells in the placenta through the interaction with a unique carbohydrate abundantly and exclusively present in the placenta. Cancer cells were found to share the same expression of this distinct carbohydrate, termed oncofetal chondroitin sulfate on their surface. In this study we have used a protein conjugation system to produce a bispecific immune engager, V-aCD3, based on recombinant VAR2CSA as the cancer targeting moiety and an anti-CD3 single-chain variable fragment linked to a single-chain Fc as the immune engager. Conjugation of these two proteins resulted in a single functional moiety that induced immune mediated killing of a broad range of cancer cells in vitro and facilitated tumor arrest in an orthotopic bladder cancer xenograft model.
U2 - 10.1038/s41419-021-03611-0
DO - 10.1038/s41419-021-03611-0
M3 - Journal article
C2 - 33824272
VL - 12
JO - Cell Death & Disease
JF - Cell Death & Disease
SN - 2041-4889
IS - 4
M1 - 353
ER -
ID: 259571723