4-1BBL fusion protein boosts T cell bispecific Abs for gastric cancer and lymphoma
INDICATION: Gastric cancer; lymphoma
Tumor-targeted 4-1BBL fusion proteins could enhance the efficacy of T cell bispecific antibodies to treat gastric cancer and lymphoma. The fusion proteins consist of a trimer of the T cell co-stimulator 4-1BBL linked to the Fc region of human IgG1 for enhanced serum stability, and a Fab fragment against CD19 or FAP expressed on malignant B cells or tumor stroma, respectively. In a xenograft mouse model of gastric cancer, the FAP-targeted fusion protein plus RG7802, a T cell bispecific mAb against CEA and CD3, reduced tumor growth and increased numbers of tumor-infiltrating CD8+ T cells compared with either agent alone. The CD19-targeted fusion protein plus RG6026, a mAb against CD20 and CD3, had the same effects in a xenograft mouse model of lymphoma...