Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy.
Nat Biotechnol
; 38(4): 420-425, 2020 04.
Article
en En
| MEDLINE
| ID: mdl-32042168
ABSTRACT
Several cancer immunotherapy approaches, such as immune checkpoint blockade and adoptive T-cell therapy, boost T-cell activity against the tumor, but these strategies are not effective in the absence of T cells specific for displayed tumor antigens. Here we outline an immunotherapy in which endogenous T cells specific for a noncancer antigen are retargeted to attack tumors. The approach relies on the use of antibody-peptide epitope conjugates (APECs) to deliver suitable antigens to the tumor surface for presention by HLA-I. To retarget cytomegalovirus (CMV)-specific CD8+ T cells against tumors, we used APECs containing CMV-derived epitopes conjugated to tumor-targeting antibodies via metalloprotease-sensitive linkers. These APECs redirect pre-existing CMV immunity against tumor cells in vitro and in mouse cancer models. In vitro, APECs activated specifically CMV-reactive effector T cells whereas a bispecific T-cell engager activated both effector and regulatory T cells. Our approach may provide an effective alternative in cancers that are not amenable to checkpoint inhibitors or other immunotherapies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoconjugados
/
Linfocitos T CD8-positivos
/
Epítopos de Linfocito T
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Citomegalovirus
/
Anticuerpos
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Neoplasias
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biotechnol
Asunto de la revista:
BIOTECNOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos