5 research outputs found
Weibs Bilder Zwei Punkt Null : Elke Albrecht, Clivia Bauer, Marianne Conrad, Katrin Prinich-Heutzenröder, Sybille Suchy, Marion Walther, Rosmarie Weinlich
- Author
- Publication venue
- Kunstverein Arnstadt
- Publication date
- 01/01/2021
- Field of study
Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy
- Author
- Albrecht Rosmarie
- Amann Maria
- Bacac Marina
- Benz Jorg
- Birk Martina Carola
- Brunker Peter
- Burgos-Rodriguez Armando G.
- Caudell David L.
- Ceppi Maurizio
- Challier John
- Chen Stanford
- Claus Christina
- Cline J. Mark
- Colombetti Sara
- Crameri Flavio
- Diggelmann Sarah
- Driessen Wouter
- Dugan Gregory
- Fauti Tanja
- Ferrara Claudia
- Freimoser-Grundschober Anne
- Gianotti Reto
- Giusti Anna Maria
- Grau-Richards Sandra
- Heinzelmann-Schwarz Viola
- Herter Sylvia
- Hettich Michael
- Hofer Thomas
- Hosse Ralf J.
- Husser Tamara
- Joseph Catherine
- Klein Christian
- Kumar Kiran
- Kuttel Christine
- Lang Sabine
- Lauer Matthias
- Levitsky Victor
- Mohan Preethi L. Bhavani
- Molhoj Michael
- Morcos Peter N.
- Mossner Ekkehard
- Nicolini Valeria
- Ongaro Amandine
- Perro Mario
- Prince Christophe
- Ringler Philippe
- Sai Solingapuram
- Sam Johannes
- Schlenker Ramona
- Stahlberg Henning
- Teichgraber Volker
- Tournaviti Stella
- Uhlenbrock Franziska
- Umana Pablo
- von Hirschheydt Thomas
- Whitlow Christopher T.
- Xu Wei
- Zippelius Alfred
- Publication venue
- 'American Association for the Advancement of Science (AAAS)'
- Publication date
- 01/01/2019
- Field of study
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 Fc gamma 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 Fc gamma R 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-gamma 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
Literaturverzeichnis
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