TY - JOUR
T1 - TCR/CD3-based synthetic antigen receptors (TCC) convey superior antigen sensitivity combined with high fidelity of activation
AU - Mühlgrabner, Vanessa
AU - Peters, Timo
AU - Velasco Cárdenas, Rubí M.H.
AU - Salzer, Benjamin
AU - Göhring, Janett
AU - Plach, Angelika
AU - Höhrhan, Maria
AU - Perez, Iago Doel
AU - Reis Goncalves, Vasco Dos
AU - Farfán, Jesús Siller
AU - Lehner, Manfred
AU - Stockinger, Hannes
AU - Schamel, Wolfgang W.
AU - Schober, Kilian
AU - Busch, Dirk H.
AU - Hudecek, Michael
AU - Dushek, Omer
AU - Minguet, Susana
AU - Platzer, René
AU - Huppa, Johannes B.
N1 - Publisher Copyright:
© 2024 the Authors, some rights reserved.
PY - 2024/9/6
Y1 - 2024/9/6
N2 - Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)–modified T cells and call for alternative antigen receptor designs for effective T cell–based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard to conveyed antigen sensitivities by up to a thousandfold. TCC-based antigen recognition occurred without adverse nonspecific signaling, which is typically observed in CAR–T cells, and did not depend—unlike sensitized peptide/MHC detection by conventional T cells—on CD4 or CD8 coreceptor engagement. TCC-endowed signaling properties may prove critical when targeting antigens in low abundance and aiming for a durable anticancer response.
AB - Low antigen sensitivity and a gradual loss of effector functions limit the clinical applicability of chimeric antigen receptor (CAR)–modified T cells and call for alternative antigen receptor designs for effective T cell–based cancer immunotherapy. Here, we applied advanced microscopy to demonstrate that TCR/CD3-based synthetic constructs (TCC) outperform second-generation CAR formats with regard to conveyed antigen sensitivities by up to a thousandfold. TCC-based antigen recognition occurred without adverse nonspecific signaling, which is typically observed in CAR–T cells, and did not depend—unlike sensitized peptide/MHC detection by conventional T cells—on CD4 or CD8 coreceptor engagement. TCC-endowed signaling properties may prove critical when targeting antigens in low abundance and aiming for a durable anticancer response.
UR - http://www.scopus.com/inward/record.url?scp=85203388372&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adj4632
DO - 10.1126/sciadv.adj4632
M3 - Article
C2 - 39231214
AN - SCOPUS:85203388372
SN - 2375-2548
VL - 10
JO - Science Advances
JF - Science Advances
IS - 36
M1 - eadj4632
ER -
