| http://purl.uniprot.org/citations/31189721 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31189721 | http://www.w3.org/2000/01/rdf-schema#comment | "Endogenous costimulatory molecules on T cells such as 4-1BB (CD137) can be leveraged for cancer immunotherapy. Systemic administration of agonistic anti-4-1BB antibodies, although effective preclinically, has not advanced to phase 3 trials because they have been hampered by both dependency on Fcγ receptor-mediated hyperclustering and hepatotoxicity. To overcome these issues, we engineered proteins simultaneously targeting 4-1BB and a tumor stroma or tumor antigen: FAP-4-1BBL (RG7826) and CD19-4-1BBL. In the presence of a T cell receptor signal, they provide potent T cell costimulation strictly dependent on tumor antigen-mediated hyperclustering without systemic activation by FcγR binding. We could show targeting of FAP-4-1BBL to FAP-expressing tumor stroma and lymph nodes in a colorectal cancer-bearing rhesus monkey. Combination of FAP-4-1BBL with tumor antigen-targeted T cell bispecific (TCB) molecules in human tumor samples led to increased IFN-γ and granzyme B secretion. Further, combination of FAP- or CD19-4-1BBL with CEA-TCB (RG7802) or CD20-TCB (RG6026), respectively, resulted in tumor remission in mouse models, accompanied by intratumoral accumulation of activated effector CD8+ T cells. FAP- and CD19-4-1BBL thus represent an off-the-shelf combination immunotherapy without requiring genetic modification of effector cells for the treatment of solid and hematological malignancies."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.org/dc/terms/identifier | "doi:10.1126/scitranslmed.aav5989"xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Chen S."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Klein C."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Lang S."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Stahlberg H."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Xu W."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Albrecht R."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Benz J."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Joseph C."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Cline J.M."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Ceppi M."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Ringler P."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Molhoj M."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Mossner E."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Umana P."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Herter S."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Brunker P."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Amann M."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Tournaviti S."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Prince C."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Ferrara C."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Perro M."xsd:string |
| http://purl.uniprot.org/citations/31189721 | http://purl.uniprot.org/core/author | "Hofer T."xsd:string |